A&P Exam 1 Flashcards
1
Q
Inside of every cell is ________ charge, while the outside of the cell is _______ charged.
A
negative, positive
2
Q
What activates a ligand gated channel?
A
the specific chemical/substance for that channel
3
Q
What activates voltage gated channels?
A
anything that alters electrical charge/membrane potential such as flow of ions to action potential
4
Q
What are the two structures around the nucleus and what differentiates them?
A
smooth and rough endoplasmic reticulum
rough has ribosomes to air in protein synthesis
5
Q
What role does the golgi apparatus play in protein synthesis?
A
“packaging plant”: puts substances in vessicles
6
Q
How many cells are in the body?
A
37.5 trillion
7
Q
What is the barrier that protects the cell from the environment?
A
Cell membrane
8
Q
How does the cell membrane protect the cell?
A
by forming a phospholipid bilayer- lipid section prevents water-soluble substances from freely moving into cell
9
Q
T/F ions/glucose can move freely in and out of the cell
A
False, they cannot due to the lipid membrane formed
glucose can to some degree
10
Q
T/F Halothane moves freely into the cell:
A
True, no longer used due to being difficult to manage
11
Q
T/F Anesthetic gases are lipid soluble:
A
True, quick onset/offset
12
Q
What allows water to move in/out the cell?
A
Aquapores (tiny): needed to allow water to move across the nonpolar cell membrane
13
Q
What determines if a substance can move across the cell membrane?
A
Permeability coefficient
14
Q
Why do ions such as Cl-, K+, and Na+ have low permeability coefficients?
A
need precise concentrations to maintain resting membrane potential/action potentials
15
Q
What are the major intracellular ions? (cations&anions)
A
C: potassium (K), A: phosphates (cholesterol, phospholipids,fats)
16
Q
What are the major extracellular ions? (cations&anions)
A
C: Sodium (Na+), A: Phosphate (P)
17
Q
What is the function of the molecular gradient of ions across the cell membrane?
A
they assist in maintaining the - inside cell /+ outside cell
18
Q
What is the function of having large cholesterol, phospholipids, and fats inside the cell?
A
major role in maintaining negativity inside cell to compensate for high levels of potassium
19
Q
What occurs to the charges inside/outside a cell when an action potential occurs?
A
charges flip/flop
inside: positive
outside: negative
20
Q
What causes the alteration of charge inside/outside cell during AP?
A
major influx of sodium causes both - influx occurs due to diffusion (passive)
21
Q
What is the role of calcium on an AP?
A
calcium enhances intracellular positivity and enters the cell AFTER it becomes positive (voltage-gated channel)
22
Q
How does calcium enter the cell during an action potential?
A
electrical change during AP stimulates the voltage gated channels to open, allowing an influx of calcium into the cell
23
Q
What is an action potential?
A
most commonly the stimulation from a cell to another cell/tissue to do something
24
Q
What are transport channels made of?
A
protein
25
What is the function of an ion leak channel?
leak channels allow a slow amount of ions to move freely to maintain balance of ions
26
What is the function of membrane proteins?
provide specificity and function to a membrane
27
How does a carrier protein work?
substance binds to protein, protein then flips around and moves the substance into the cell
28
What are the two ways to transport across the cell membrane?
Diffusion: passive
Active Transport: requires energy
29
What drives diffusion to occur?
concentration gradient: always moves from high to low
30
What type of transport must be used when moving an ion against it's concentration gradient?
active transport
31
What is required to fuel active transport?
ATP (energy source)
32
What structures allow return to baseline following an action potential?
aquaporins, aquaglyceroporins, ion channels
33
O2, N, CO2, alcohols, and phenols are examples of:
lipid soluble substances (moves freely across cell membrane)
34
What would occur when confining the space of fluid molecules?
increased energy, increased pressure
35
What substances can move via aquaglycerporins?
glycerol, urea, ammonia
36
What determines what substances pass through an ungated ion channel?
size, shape, and charge of channel/ion
37
What are the two ways gated channels are regulated?
voltage or chemical/ligand
38
How are potassium channels selective?
the channels are lined with carbonyl oxygens that strip the water off the potassium molecules, sodiums dont reach the carbonyl oxygens and end up being too large to pass through
39
How are sodium channels selective?
the channel is lined with negatively charged amino acids (glutamate) which attract na, k is too large
40
Which channel functions in an "all or none" manner?
voltage gated channels
41
T/F a lipid soluble molecule can facilitate transport of inorganic ions across the lipid bilayer?
true
42
Would you call ionophore transport of ions simple diffusion or facilitated diffusion?
facilitated diffusion carriers
43
What is the difference between simple and facilitated diffusion?
simple diffusion is driven solely on concentration gradient and there is no max/ceiling of movement that can occur at a time.
facilitated diffusion still relies on a concentration gradient but requires a protein channel for the substance to move across the membrane. so # of protein channels = limiting factor/max movement
44
What is the Vmax?
maximum concentration that can be moved across cell membrane
45
What is another term for facilitated diffusion?
carrier-mediated diffusion
46
Rate of diffusion is limited by:
number of carrier proteins and Vmax of the carrier protein (pmol/min/mg protein)
47
Diffusion is driven by:
concentration gradient
48
How should the concentration difference be calculated for diffusion?
concentration outside - concentration inside
49
What are the factors that affect net diffusion?
1. concentration difference
2. electrical potential
3. hydrostatic pressure difference
50
T/F energy of molecules can cause them to move AGAINST concentration gradient
true, but not super frequently
51
Net diffusion messures:
how many molecules were moved from high to low concentration
52
Other than diffusion, what else moves ions?
electrical charge: will draw opposite charge (like charges repell)
53
What is Nernst Potential/Equation?
theoretical intracellular electrical potential that is = in magnitude but opposite in direction to the concentration (chem) force
basically equal charge/concentration equilibrium (resting membrane)
54
When will the net inward current of positively charged molecules become zero?
when the electrochemical equilibrium has been achieved
55
What are the two things that can move a cell from the point of equilibrium?
1. change in ion concentration
2. change in electrical charge
56
What occurs when hydrostatic pressure increases?
increased pressure causes an increase in energy which is then used for movement from high to low concentration to occur
57
What are the two types of active transport?
Primary and Secondary
58
What is active transport?
movement of an ion against concentration gradient (requires energy source such as ATP)
59
What is used as the energy source for Primary active transport?
ATP is directly used as energy for work
60
How does Secondary active transport occur?
it is driven by energy stored in the electrochemical gradient of another molecule (usually Na+)
indirect used of energy
61
What Primary active transporter is found in every cell of every tissue of the body?
Na-K-ATPase pump
62
What is the movement of Na and K via Na-K-ATPase pump?
3 Na's out, 2 K's in
63
What is the deeper reason for the Na-K-ATPase pump?
It works to restore cellular resting membrane potential. (negative charge)
64
What occurs to K when Na rushes into the cell during an action potential?
It leaks out of the cell via leak channels... so they can be used in the Na K ATP pump
65
How does Digoxin work?
inhibits na k pump which results in ^ intracellular Na+ (decreased gradient)
decreased Na/Ca antiporter
intracellular Ca+2 increases
increases contractility
66
Muscle AP is driven by ______ not sodium.
Calcium
67
Apart from restoring ion concentration/gradient in cell, what else does NA K pump manage?
Osmotic Balance: moving na out decreases intracellular volume and thus, is activated by increased intracellular volume
68
How much energy does NA K pump require?
1/5 normal cells energy, 2/3 nervous cells energy
69
What are the two other types of primary active transporters?
Ca2+ATPase, H+ ATPase
70
What are the two active transporters present in the cell membrane of muscle fibers?
1. Na K pump
2. Ca2+ pump (also in the sarcoplasmic reticulum)
71
How does the Ca2+ ATP pump contribute to a muscle fiber?
maintains low cytosolic Ca2+ concentration
72
Where are the 2 locations H+ ATPase pumps found?
1. Parietal gastric gland cells (HCl secretion)
2. intercalated cells of the renal tubule (controls pH)
73
In the setting of metabolic acidosis, what occurs with the H+ ATPase pump in the kidneys?
dumps out Hydrogen ions to assist in restoring normal pH
74
How does the H+ ATPase pump work?
concentrated H+ ions up to 1 million-fold.
free hydrogens = acid
carbonic acid-bicarbonate buffer system uses H and HCO3 to manage/balance pH at a cellular level
75
What is the most important chemical process that occurs in the body?
carbonic acid-bicarbonate buffer system
H2O + CO2 <> H2CO3(carbonic acid) > H+ + HCO3
drives respiratory rate and tissue perfusion (O2/CO2)
76
How is most of the CO2 produced in the body returned to the lungs?
by combining with H2O to form carbonic acid then transformed into H+ + HCO3, then chemical process is reversed and CO2 and H2O is exhaled
77
What is required for secondary active transporters to work?
an electrochemical gradient (and stored energy)
78
Secondary active transporters use protein cotransporters called _______ and ________.
Antiporters & symporters
79
What is the difference between antiporters and symporters used in secondary active transport?
Antiporters move in opposite directions while symporters move in the same direction
80
How do symporters work?
They use energy from a "driver" ion such as sodium to move both na and another substance in the same direction
81
What transporters works by transporting substances in opposite directions, using "driver" ions like sodium?
Antiporters (one from intracellular, one from extracellular)
82
Where does *transcellular* transport of glucose and amino acids frequently occur?
Epithelial cells of GI tract
83
How does transcellular transport work?
Cell absorbs substance from the lumen then transports substance on the other side into a vessel or interstitial tissue/space
84
Osmosis is the net diffusion of:
Water
85
What drives the movement of water during the process of osmosis?
moves down concentration gradient (usually +2 elemenets)
86
Osmotic pressure can be defined as:
The pressure required to counter osmosis
(usually attributed to the osmolarity of a solution)
87
What stops osmotic pressure from drawing water into a solution?
it stops when a balanced state is achieved
88
What is tonicity?
the impact on osmolality in relation to a cell
89
What is an *Osmole* of a substance?
the molecular weight of a substance, same as a mole technically.
an osmole is the "drawing" ability of a solution
90
What are examples of isotonic solutions and why are they used first line?
0.9% NS and Lactated Ringer's
there is equal tonicity between the fluids and the cells, thus will not cause an alteration in the cellular fluid/volume status which could cause harm
91
Which two types (tonicity) of fluids have a cellular impact?
Hypertonic (shrink cells)
Hypotonic (swell cells)
due to osmotic pressure moving water into the cell
92
Causes of hyper/hypo natremia:
hyponatremia: ^ h2o ingestion, SIADH
hypernatremia: excess h2o loss/sweat, central/nephrogenic DI
93
If you have a higher osmolality inside the cell than outside, which way will h2o move and why?
water will move into the cell in attempt to achieve an equilibrium state.
94
What is the difference between diffusion and osmosis?
Diffusion: can only move particles to achieve equal state
osmosis: can only move water to achieve an equal state
95
What are the two processes that assist the cell in returning to resting membrane potential?
Na K pump and Leak channels
96
In the Na and K leak channels, what prevents the ions from diffusing to the point of equilibrium?
Charge on the inside of the cell becomes "negative enough" to attract potassium and prevent it from diffusing out regardless of concentration gradient (Nernst equation)
97
The electrical potential that counters net diffusion of K+ is called:
K+ equilibrium potential (this refers to one element alone)
98
What are the Electrical potentials for both K and Na?
K: -94
Na: +61
at resting membrane state
99
What is Vm and why is it so close to Ek?
resting potential- because the membrane is far more permeable to k than na (100x more permeable) also 100x more leak channels
100
What is the difference in transporters for sodium and potassium?
Potassium transporters are lined with carbonyl oxygens while sodium transporters are lined with negatively charged amino acids (glutamates)
101
What is the major point regarding the Goldman-Hodgkin-Katz equation?
Resting membrane potential will always be closest to the equilibrium potential for the ion with the highest permeability. (totally independent of concentrations)
102
What is the resting membrane potential for skeletal muscle fibers?
-85 to 95mV
103
What is the resting membrane potential for smooth muscle fibers?
-50 to -60mV
104
What is the resting membrane potential for astrocytes?
-80 to -90mV
105
What is the resting membrane potential for Neurons?
-60 to -70mV
106
What is the resting membrane potential for Erythrocytes?
-8 to -12mV
107
What is the resting membrane potential for Photoreceptor cells?
-40mV (dark) to -70mV (light)
108
Why is the resting membrane potential for Erythrocytes so close to 0mV?
Because they are so permeable to water (and thus sodium)
109
What is the net drawing force of an ion?
the difference in millivolts between the membrane potential and the equilibrium potential for that ion
110
What is the rationale for having different net driving forces for different ions?
This allows them to move in and out of a cell at different rates due to this force which allows the cell to reach specific electrical membrane "goals"
111
What would occur if Na had the net driving force of K?
It wouldn't rush into the cell once membrane potential reaches threshold as it does.
112
What is an overshoot of an action potential?
Means to become "too positive" above 0mV, occurs because Na gates dont always close soon enough
113
What occurs when we reach "threshold" in a cell?
The inside becomes more positive
114
What is another term for being at resting potential?
Polarized
115
What is the term used for the phase that occurs between resting (polarized) state to threshold?
Depolarization (move more positive)
116
What is the ion movement that causes depolarization?
Na movement into the cell
117
Why can slight stimulus occur without yielding an action potential?
They do not reach "threshold" state (not depolarized enough to cause an action potential)
118
What is threshold typically in relation to resting?
15-20mV less or more positive
119
What occurs to the na gates at threshold?
All voltage gated Na channels are instantly wide open, allowing Na to rush in and depolarize the cell
120
What causes Na channels to close after an AP occurs?
0mV charge closes the voltage gated channels
121
At 0mV, when Na gates close, what else occurs?
K gates open, potassium flows out, causing cell to become more negative which leads to repolarization
122
What 2 things cause repolarization after an action potential occurs?
1. K gates open, potassium moves out
2. Na K pumps- 3 Na out, 2 K in
123
Hyperpolarization is the opposite of:
Overshoot
124
What causes hyperpolarization?
resting membrane becomes too negative due to voltage gates closing slightly after the trigger at -90mV
125
What fixes hyperpolarization and restores resting membrane potential?
K leak channels (more of these- greater impact)
Na K Pump (removes Na from inside/restores balance)
126
Repolarization brings cell membrane:
back to resting potential
127
What must be reached for an action potential to occur?
MUST REACH THRESHOLD
128
What are the effects of depolarization on a cell?
Excitation
129
What are the effects of hyperkalemia on threshold potential and cell excitability?
hyperkalemia increases positive charge inside and outside the cell this brings the cell's resting membrane much closer to threshold which causes cells to be much more excitable (smaller stimulus needed)
130
What is the effect of low plasma calcium on the threshold potential?
threshold becomes more negative and thus closer to Vm. This increases the excitability of the cell.
131
What role does calcium play in resting membrane potential?
Calcium impacts na pump function (less positive charges outside cell) more negative outside which is closer to normal membrane potential
132
What two electrolyte alterations can cause cells to be hypersensitive to action potentials?
Hyperkalemia (increased membrane potential)
Hypocalcemia (decreased threshold)
133
Why do you give calcium in the setting of hyperkalemia?
to drive potassium back into the cell and increase threshold to prevent hyperexcitability
^ K takes Vm to -80mV, -75mV is threshold = arrhythmias. giving calcium increases threshold from -75mV to -65mV to widen that gap between resting and threshold to prevent ectopy
134
How does low sodium in blood cause muscle tetany?
low calcium increases excitability of nerve axons by causing sodium channels to open following very small increases in Vm
135
The regenerating depolarization of membrane potential that propagates along an excitable membrane is defined as:
an action potential
136
An action potential cannot occur unless:
Membrane potential reaches threshold (depolarizes- all or nothing)
137
Calcium affects ______, while sodium and potassium affect _______ ________.
Threshold, membrane potential (ca also affects how sodium exits cell)
138
How long does it typically take for an AP to occur?
1 millisecond
139
What are the 5 basics of action potentials?
1. all-or-nothing (to reach threshold)
2. constant amplitude (do not summate- frequency not amplitude)
3. initiation by depolarization
4. involve changes of permeability
5. rely on volt. gated channels (na in skeletal, ca in cardiac)
140
________ potential is closer to the _______ potential that is more _________ in the cell membrane.
resting | equilibrium | permeable
141
What can stop an action potential from occurring once it reaches threshold?
absolutely nothing
142
How is the process of a cardiac action potential different than skeletal muscle?
It is primarily driven by calcium rather than sodium, calcium channels close much slower which causes a "plateau" phase (refractory)
143
Is conduction velocity of an action potential constant or varying?
Conduction is constant, this is true for any given fiber
144
What factors alter conduction velocity of an action potential?
myelination/demyelination
diameter of fibers/type of fibers (sensory quality)
145
What type of fibers are better conductors?
myelinated fibers
146
What type of fibers conduct pain sensations?
unmyelinated C Fibers
147
_____ permeability increases during the upstroke of an action potential.
Sodium, this assists in allowing a depolarization to occur by attracting sodium when all the gates open- thus resulting in a greater impact
148
What initiates the increase of sodium permeability during the upstroke of an AP?
stimulus such as a voltage change or impulse
149
During the upstroke of an AP is the membrane potential closer to Ek or Ena?
Ena due to the increased permeability to sodium during that phase.
150
What occurs to membrane permeability during the downstroke of an action potential?
na permeability decreases, k permeability increases due to opening of k channels
151
During the downstroke of an AP is the membrane potential closer to Ek or Ena?
Ek due to increased k permeability
152
What is the difference between *Absolute* refractory period and *Relative* refractory period?
impossible for AP to occur during absolute due to voltage inactivation of Na channels, can occur during relative but must have a lot of stimulation
153
What is the purpose of having a refractory period?
refractory periods limit the maximum frequency of APs
154
How does propagation of an action potential occur?
opening of na channels generates a local current that depolarizes adjacent membranes, allowing more na channels to open and travel accordingly.
155
What cells produce the myelin sheath of a nerve?
Schwann cells- surround nerve axon which forms the sheath
156
How does sphingomyelin work?
decreases membrane capacitance and ion flow 5000-fold (insulates) to speed conduction
157
How does a nerve impulse travel along a myelinated nerve axon?
it jumps to nodes of Ranvier rather than traveling the entire length of the nerve axon
158
What is the name of the structures on the myelin sheath used for conduction?
the sheath is interrupted every 1-3mm by a *node of Ranvier*
159
What is saltatory conduction?
term used for APs jumping from node to node (na channels are more concentrated at these areas), increased velocity, and conserves energy
160
What is a synapse?
point of communication between cells. (commonly at least one nerve cell) also usually involves transmitter substances- can be inhibitory or excitatory
161
What part of the target nerve cell does the synapse occur on?
Dendrite
162
An action potential in the _____ cell causes a transmitter to be released.
presynaptic
in fast synapses, substances bind to receptors on postsynaptic cells to directly open ligand gated channel
163
Excitatory transmitters _______ membrane, while inhibitory transmitters _______ membrane.
depolarize, repolarize?
164
What is an example of a medication that is used to *inhibit* APs r/t pain sensations?
lidocaine
165
What is Excitatory Post Synaptic Potential (EPSP)?
electrotonic response that decays with an exponential time course. makes it more sensitive to stimulation (encourages AP to occur)
166
What are the two types of EPSPs?
temporal summation: multiple electrical impulses at same synapse
spatial summation: multiple electrical impulses from different synapses at the same time
167
What ions are involved with EPSPs?
cations and Na channels
168
Which type of EPSP occurs when there are multiple impulses from the same synapse?
Temporal summation
169
Which type of EPSP occurs when there are multiple impulses coming from different synapses?
Spatial summation
170
What are Inhibitory Post Synaptic Potential (IPSPs) and while ions are associated?
postsynaptic cell is hyperpolarized, thus decreases possibility for an AP to occur. can summate
Ions: K or Cl
171
What physiological change allows EPSPs and IPSPs to occur?
alterations in membrane permeability to ions- consider equilibrium potentials.
172
What are examples of ligands that are used in synapses?
Acetylcholine, norepinephrine, epinephrine, serotonin, dopamine, glycine, glutamate, adenosine
173
GABA is an _______ neurotransmitter that works by ______ post synaptic cell
inhibitory, hyperpolarizes (depresses excitability)
174
Glutamate is an example of a _______ neurotransmitter that works by _______ post synaptic cell
excitatory, depolarizes (enhances excitability)
175
What causes the automaticity of cardiac cells?
independent na leak channels that allow na to move into the cell to initiate an AP
176
What occurs during Phase 0 of ventricular tissue AP?
Depolarization: inward flow of Na
177
What occurs during Phase 1 of ventricular tissue AP?
Early repolarization: out flow of K
178
What occurs during Phase 2 of ventricular tissue AP?
Plateau phase: inward Ca/Na current, decrease in k outflow
179
What occurs during Phase 3 of ventricular tissue AP?
Repolarization: outward K current
180
What occurs during Phase 4 of ventricular tissue AP?
Resting potential
181
Movement of what ions contributes to the plateau phase in ventricular tissue?
Calcium: in/Sodium: in
Potassium: out
182
What are the 3 phases of the SA node cell?
0: depolarization- ca in
3: plateau- k out
4: slow depolarization- na in
183
How does the PNS decrease heart rate?
by altering SA node cell membrane permeability to K decrease effects of sodium leaking into the cell to allow depolarization/ opposite occurs in SNS w/ Na/C
184
What are the smaller functional units of the muscle?
Fascicle
185
What are muscle fascicles made of?
muscle fibers (has own nucleus)
186
What are muscle fibers made of?
Myofibrils
187
What are the two primary structures that make up myofibrils?
Actin: light chain, Myosin: dark/heavy chain
188
What causes muscle striations?
bands within myofibrils that contain varying amounts of actin and myosin
189
One Z-disk to the next Z-disk is one:
Sarcomere
190
What is the functional structure of the muscle?
Sarcomere
191
Heavy chain fibers are called ________, and light chain fibers are called ________.
Myosin, Actin
192
What are the two functional structures of myosin?
tail (light chain) and head (heavy chain)
193
What is the structure that covers the sarcomere?
Sarcolemma
194
_________ fibers are multinucleated, single cells.
muscle
195
___________ are contractile elements of the cell that are covered by the sarcoplasm.
Myofibril
196
In a sarcomere, the _____ in a thin fiber, and the _____ is a thicker fiber.
Actin, myosin
197
Which fiber in the sarcomere is directly attached to the Z-disk?
Actin
198
What must occur to a sarcomere for a contraction to occur?
it must shorten
199
What structure is between the actin strands?
Myosin
200
What makes up an I-band?
ONLY Actin (thin, white/clear fibers)
201
What is the significance of the M line?
it is the middle of the sarcomere
202
What structures make up the H zone and where is it?
Pure myosin, area in the middle of the sarcomere before attachment of myosin/actin
203
What structures make up the A band and where is it?
Actin AND Myosin, area until myosin strands end
204
Which line and zone of the sarcomere contain only myosin?
M-line and H-zone
205
Which two structures of the sarcomere are most important and why?
Z-disk and I-band, for contraction to occur, the the I-band will shorten
206
What is the major purpose of the different zones and bands of the myofibrils?
They assist in microscopically identifying different parts of the fiber
207
What is the function of Titin, what is it connected to?
the largest protein in the body with 3,000 molecular components.
connected to Z-disk and Myosin
functions as a spring that allows Z-disk to recoil properly after contraction. (passive elasticity) also called Connectin
208
What is the functional length of the sarcomere and why does that matter?
2.2mm, when length exceeds there is a decrease in tension on the muscle fiber which decreases the contractility due to less myosin/actin contact
209
What is the difference between isotropic and anisotropic?
Isotropic: appearing light
anisotropic: appearing dark
210
A sarcomere is made of a complete ____ band and the 2 halves of the ___ band which are adjacent to it.
A, I
Note: Z disk delimits the sarcomere BUT the Z disk is in the middle of an I band!!!!!
211
_____ is commonly referred to as a thin filament, while ______ is referred to as a thick filament.
Actin, myosin
212
What is the difference between the I band and the A band?
I band contains only actin while the A band contains the middle section of the myosin and the actin that is connected
213
Based on the composition of the I band and the A band, what color should they be?
I band: light (actin)
A band: dark (myosin)
214
Which band of the sarcomere changes during muscle contraction?
I band: only the actin can technically "move"
A band cannot shorten due to myosin content
215
When the I band is pulled into the A band, the I band is:
Obscure (moves across myosin [A band], so the band is no longer visual)
216
__________ results from the sliding of interdigitating actin and myosin filaments.
contraction
217
Actin and ______ twist together to form a rope. Why?
Tropomyosin, functions to cover active sites on actin to prevent constant binding/contraction
218
What is the function of Tropomyosin and what is it attached to?
It is attached to actin, functions by covering the active binding sites
219
What are the 3 parts that make up an actin filament?
1. F-actin (double-stranded helix)
2. Tropomyosin
3. Troponin
220
What are the 3 protein units that form troponin?
1. Troponin I- binds to actin
2. Troponin T- binds to tropomyosin
3. Troponin C- binds to calcium
221
What makes up the myosin molecules?
2 heavy chains: tail
4 light chains: head (site of ATPase activity)
222
Where on the molecule does ATPase activity occur?
The Head (light chains) of the molecule
223
What is the purpose of ATP for the myosin molecule?
It allows the myosin head to use ATPase to break off a phosphate group which results in energy release to "cock" the myosin head back for attachment/walk-along contraction to occur
224
Where is the ATP receiving site in the myofibril?
Myosin head
225
Explain the steps that cause the Powerstroke of contraction:
1. Calcium is released- binds to Trop C
2. Conformational change to Tropomyosin occurs
3. Exposes myosin active binding sites on actin
4. Myosin binds ATP- breaks off phosphate, moves off the head, cocks myosin head (uses the ATP energy)
5. Myosin attaches to Actin, pulls and fires = powerstroke- occurs over and over again
multiple myosin heads w/ their own ATP, heads need new ATP for each powerstroke
226
What causes Rigor Mortis to occur?
There is no ATP which causes the myosin head to be "stuck" to the actin strand, prevents muscle relaxation, decreases as tissue necrosis occurs (occurs quickly with ^ heat/temp)
227
What factors affect the degree of contraction?
Amount of stimulus
Amount of calcium released
228
How does low/lack of calcium affect contraction?
Prevents conformational change of tropomyosin, thus active binding sites on actin remain covered = directly preventing myosin from binding.
229
What is the difference between passive and active tension?
Passive: "pulling slack" without stretching. slight exertion/tension. as ^^^^ causes active
Active: stretching muscle, requires more work
230
Can degree of tension on a muscle be 0?
technically only if a muscle is fully flaccid in the setting of some type of spinal cord injury
in a healthy individual no: muscle tone must somewhat remain
231
What is the relationship between active tension and muscle lengthening?
Active tension decreases linearly as length increases AND decreases
232
The ______ myosin head that can attach to actin causes a _______ of tension.
more, increase
less, decrease
Thus greater contraction
233
Why can't a short sarcomere create large amounts of tension? (2)
1. small distance available to move already contracted z-disk
2. counteropposion of the myosin heads attempting to move actin strands "against" each other- less heads in contact with actin
234
The ______ the sarcomere the ________ contraction, until it _______ the amount of actin/myosin head contact.
longer, greater, exceeds
contact must occur for great strength of contraction
235
What is the concern related to the contraction and tension of a very long sarcomere?
decreased tension could be produced during contraction if there is poor actin/myosin head contact
236
What occurs to the cardiac sarcomeres in dilated cardiomyopathy
They are stretched so much that it decreases actin/myosin head contact, decreases tension, thus decreasing strength of contraction
237
What is the relationship between load to velocity of contraction?
Increasing the load causes an increase in velocity, proportionally
238
What is the difference between isotonic, isometric, concentric, and eccentric contractions?
isotonic: muscle contraction w/ length change
isometric: muscle contraction w/o length change
concentric: isotonic contraction w muscle shortens
eccentric: isotonic contraction w muscle lengthens
239
Can you build muscle without shortening/lengthening of the muscle?
yes, by using isometric contraction- no change of muscle length occurs, via a stabilizing force increases stress/tension on the muscle
240
Why is stretching important?
lengthening/elongating the sarcomeres prevents the formation of contractures and builds muscle strength,
stretching a lot increases I-band room which increases contractility
also realigns muscle fibers
241
Why are your muscles less strong when actively stretched?
muscle fiber is pulled to it's full length which decreases myosin/actin contact, connective tissue takes up the slack
242
How do Fast/Slow muscle fibers differ in their function and thus, overall structure?
Different resistance to fatigue
Fast 2: large diameter, white, rapid cross bridging, high Vmax, high glycolytic enzymes, low myoglobin content, low capillary density/mitochondria
Slow 1: small diameter, red, color from lots of myoglobin (oxidated), dense blood supply, slow cross-bridging, low Vmax, low glycolytic enzyme content, lots of mitochondria
243
What determines the speed of contraction of a muscle?
Vmax of the myosin ATPase
244
Long distance runners have a higher percentage of what type of muscle fibers and why?
Slow twitch muscle fibers develop because the distance training causes cellular biogenesis of greater formation of mitochondria to supply the tissue demand. high levels of fast to slow twitch transformation with intense training
245
What structures make up a motor unit?
A collection of muscle fibers that are innervated by a single motor neuron
1. somatic motor axon (nerve)
2. muscle fibers
3. neuromuscular junctions: direct attachment
246
What are the two different types of muscle force summation?
1. Multiple fiber summation: many fibers sending an impulse via different motor units (spatial)
2. Frequency summation: increased frequency of contraction from a single motor unit (temporal)
247
What is force summation and what can it eventually lead to?
increase of contraction intensity due to added individual twitch contractions can eventually cause tetanization- a solid state of contraction bc fast impulse where calcium remains inside
248
What is the size principle of multiple fiber summation r/t muscle contraction?
motor units are recruited from smallest to greatest and type 1 to type 2
249
What is resting muscle tone?
muscle tone is a state of partial contraction, keeping them firm rather than fully flaccid such as in the setting of paralysis/nerve injury
250
How allows muscles to achieve "resting muscle tone"?
nerve impulses from brain stimulate fibers to contract to remain tone, these signals also can originate in the muscle spindles
involuntary process BUT increased exercise increases degree of muscle tone
251
T/F PNS innervation can cause muscles to become flaccid, losing natural tone
FALSE, must inhibit SNS to decrease/inhibit tone because the PNS has NO innervation
252
What are the 4 types of muscle growth remodeling?
1. Hypertrophy
2. Hyperplasia
3. Hypertrophy & Hyperplasia
4. Lengthening
253
How does muscle hypertrophy occur and how long does the process take?
caused by near max force development, thickens actin and myosin, then myofibrils split
occurs commonly within weeks
254
How can hypertrophy and hyperplasia be differentiated?
hypertrophy is usually the enlargement of pre-existing muscle fibers, while hyperplasia is an increased number of muscle fibers (additional)
255
How does muscle hyperplasia occur and how common is it?
it is the rare process of new muscle fiber formation which can be caused by endurance training
256
What is the result if both hypertrophy and hyperplasia occurs?
there is an increase in force generated by the muscle, no change in shortening capacity of max velocity of contraction
257
What are the effects of muscle fiber lengthening?
occurs with normal growth, no change in force, increased shortening capacity, increased maximum contraction velocity
sarcomeres must grow (as children get older) to reach strength potential
258
Why does increasing the number of sarcomeres in a series lead to a faster velocity of shortening?
add the velocity of m/sec to equal total movement/work.
eight sarcomeres will complete 2x velocity of four
259
What are the two types of atrophic muscle remodeling?
1. Atrophy: due to denerve/neuropathy, cast, lack of gravity
2. Atrophy with fiber loss: occurs in longer periods, very difficult to replace lost fibers
260
What is a muscle fasciculation?
involuntary muscle contraction/relaxation
usually due to low magnesium intake
261
how does hypomagnesemia cause muscle fasciculations?
magnesium ions block neurosynaptic transmission by interfering with acetylcholine release
262
How can deep muscle fasciculations be sensed and what is the significance?
Electromyography (EMG) useful in assessing the effect of blocks
263
A neuromuscular junction is a specialized ________ between a ________ and a _________.
synapse, motorneuron, muscle fiber
264
When the neuromuscular junction occurs at a structure on the muscle fiber it is called the:
Motor end plate (usually one per fiber)
265
What is the synaptic trough of the neuromuscular junction and what important structures lie in it??
the invagination of the motor end plate, where the axon terminal and the target tissue meet
trough contains Subneural Clefts
266
What is the importance of the subneural clefts in the neuromuscular junction?
they increase surface area of the postsynaptic membrane which increases the amount of receptor sites. SC is 20-30nm wide
267
What is the importance enzyme that can be found in the synaptic cleft and what is it's purpose?
Acetylcholinesterase (AChE), removes the acetylcholine (ligand) from the receptor to stop influx of na into cell, thus stopping the AP/reaction
268
What structures lie in the subneural clefts?
ach (ligand) gated channels at the top of the cleft and na (voltage) gated channels at the bottom of the cleft
269
Why are there two different kinds of channels in the subneural clefts?
ach (ligand) needs to bind to it's receptor to alter the voltage by allowing some type of positive charge to enter which depolarizes and opens the na receptor to let a LOT of na enter.
270
What structure forms cellular vesicles?
Golgi Apparatus
271
What are the 3 steps that lead to the release of ACh from the motorneuron?
1. AP begins in ventral horn of the spinal cord
2. local depolarization opens volt gat Ca2+ ch
3. increase of cytosolic Ca2+ triggers vesicles to fuse w/ membrane and release ACh via exocytosis
272
What are dense bars in skeletal muscle?
areas of increased concentration of materials (ca2+ channels on both sides and vesicles on other sides)
273
How is the ACh gated channel selective to allow movement of cations?
It is lined with negative charges
274
What terminates the process of spreading APs?
Acetylcholinesterase (prevents constant contractions)
275
How do inhibitors such as curariform (Curare) drugs work?
Block nicotinic channels/competitive, preventing contraction
276
How do stimulate drugs such as nicotine work?
They increase gated activity because Acetylcholinesterase is ineffective
277
What is an indication for an Anti-AChE drug and how do they work?
Parkinson's can be treated with neostigmine to assist with movements by blocking the degradation of ACh and prolonging it's effects
278
What are the effects of atropin on sarin gas and why?
atropine blocks muscarinic ACh receptors (muscle has nicotinic)
Stops seizures and convulsions- treats side effects, not the major issue
279
Where is Calcium stored in skeletal muscle?
Sarcoplasmic reticulum
280
What are T-tubules in skeletal muscle?
Invaginations in the sarcolemma that penetrate the muscle fiber (usually at Z-disks), to assist in transmitting APs deep into the muscle fiber
281
What structure inside the T-tubule assists in AP movement?
Dihydropyridine (DHP) receptor
282
Where is the Dihydropyridine (DHP) receptor located and what is it connected to?
inside T-tubule, connected to the ryanodine receptor
283
What is the function of the Ryanodine (RyR) receptor?
When stimulated (from AP movement), it opens the Sarcoplasmic reticulum to allow calcium to flow into the cell to attach to Troponin C to allow contraction to occur
Ca release is PROPORTIONAL to membrane voltage
284
What ion "activates" dihydropyridine (DHP) activity?
Na movement
285
Once contraction ends, how does calcium move back into the Sarcoplasmic reticulum?
Calsequestrin is a large protein body inside the sarcoplasmic reticulum that basically attracts calcium to move back into SR
286
What activates Calsequestrin/calcium attraction?
Voltage/concentration process
287
What Deactivates Ryanodine (RyR) receptor?
Loss of AP
288
What is the trigger of calcium release for Skeletal and Cardiac muscle? (VACR/CACA)
Skeletal m: SR trigger to release Ca is Voltage
Cardiac m: SR trigger to release Ca is Ca
289
What activates DHP receptor: Skeletal vs Cardiac
S: T-tubule voltage sensor
C: T-tubule ca channel receptor
290
The cardiac muscle ryanodine receptor is _____ (ion) gated and ____ release is __________ to calcium entry.
Calcium
Calcium
proportional
291
What causes Malignant Hyperthermia to occur?
Constant leak of calcium out of ryanodine "plug" that is triggered by gases/succs
292
What are the two types of smooth muscle?
1. Unitary (more common)
2. Multi-unitary
293
What are examples of Unitary and Multi-unitary smooth muscle groups?
Multi-unitary: muscles in the iris
Unitary: smooth muscle in intestines
(sheets of muscle)- syncytial, work together
294
Which type of smooth muscle is most commonly seen and is in the GI tract and is commonly referred to as the visceral type?
Unitary: contract together as one unit, syncysually together
295
What type of muscle tissue does not have striations?
Smooth muscle
296
T/F smooth muscle functions totally different than skeletal muscle regarding actin/myosin
False, same structures are there. just like a fish net (contracts on self)
297
What are the special features of smooth muscle contraction?
1. fibers are able to shorten by 60-75% due to structural formation (contracts on self)
2. dense body anchor points + intermediate filaments
3. actin/myosin contact + dense bodies allow the special compression type of contraction in multiple directions
298
What smooth fiber mechanism allows the muscle to remain contracted with little energy consumption for long periods of time?
"Latch" mechanism/unique fiber structure that allows compression/contraction to remain from hours to days
299
What structure acts as the Z-disk of a smooth muscle fiber?
Dense body
300
What structure of smooth muscle fibers provides structure to the fiber by connecting to the dense bodies?
Intermediate filaments
301
What muscle(s) is myogenic and what is this definition?
Smooth muscle, cardiac muscle
spontaneously active/can generate own AP
302
What ion triggers APs in smooth muscle?
Calcium
303
What is true regarding smooth muscles and their relationship with calcium?
They have poorly developed Sarcoplasmic Reticulum which do not contain much calcium. For an AP to occur, they depend on (extracellular) calcium to enter the cell which then encourages release of SR calcium
304
How does the neuromuscular junction of smooth muscle differ from that of skeletal muscle?
The nerves are not in direct contact with the muscle fibers, there is a juncture (matrix space). The nervous tissue has varicosities
305
What type of muscle tissue has varicosities on it's neuromuscular junction?
Smooth muscle
306
In skeletal muscle, neurotransmitters are secreted in ____ while in smooth muscle, neurotransmitters are secreted by _________.
Vesicles, Varicosities
307
__________ is the primary neurotransmitter for PNS, __________ is the primary neurotransmitter for SNS.
Acetylcholine, Norepinephrine
308
What protein allows smooth muscle to function without Troponin?
Ca from ECF/SR binds to Calmodulin which then produces myosin light chain kinase (MLCK)
309
When extracellular Calcium moves into the cell what occurs?
It triggers calcium release from the Sarcoplasmic Reticulum, BUT primarily depends on extracellular calcium to function appropriately
310
What are the effects of hypocalcemia on smooth muscle contraction?
Can actually prevent contraction from occurring because smooth muscle is heavily reliant on extracellular calcium to contract
311
How does smooth muscle contract/relax without troponin?
Calcium binds to calmodulin which produces MLCK (myosin light chain kinase) which uses ATP to phosphorylate the myosin head which is required for actin bind/contraction to occur
312
What are the effects of myosin light chain kinase (MLCK) on smooth muscle contraction?
MLCK uses an ATP molecule to phosphorylate the myosin heads which provides the myosin heads with "stored" energy which provides needed energy to bind with actin, "cock" the head back, and contract
313
Since MLCK phosphorylates myosin heads in smooth muscle, leading to contraction, what allows relaxation?
Yet another enzymatic process involving myosin light chain phosphatase which dephosphorylates/removes phosphate group from the myosin head (uses another ATP)
314
What two enzymes are needed for smooth muscle cross-bridge cycling to occur?
myosin light chain kinase and myosin light chain phosphatase (each uses 1 ATP molecule)
315
What regulates function of myosin light chain phosphatase in smooth muscle?
CALCIUM
316
What two types of action potentials can occur in smooth muscle?
1. Repetitive spike potentials
2. Plateau AP (uterus): long, controlled with variations in strength
317
What are the 4 systems that control smooth muscle?
1. Paracrine: histamine reaction, cell-cell
2. Endocrine: epinephrine release, ADH
3. Autonomic nervous system: norepi
4. Local nervous system: enteric system
318
What structure allows smooth muscle fibers and cardiac muscle fibers to work together?
Gap junctions: allows FAST transmission of AP/ions to neighboring cells
319
The _____ side of the heart is the _______ pressure pump with the _____ side of the heart is the ______ pressure pump.
right, low (deox)
left, high (ox)
320
What are the 4 layers of the pericardium? out -> in
1. Fibrous pericardium
2. Parietal pericardium
3. Pericardial space
4. Epicardium (visceral pleura)
321
Why do cardiac muscle fibers branch?
branching allows interweaving of cells, allowing ^ in contraction due to ^ surface area
322
Why do cardiac muscle fibers have intercalated disks?
Kinda like anchoring points (Z-disks, dense bodies) but with gap junctions (to allow pass of AP/ions)
323
What is the resting membrane potential of cardiac muscle?
-85 to -95mV (AP = 105mV)
324
What is a *key* difference regarding the difference between the action potential of a cardiac muscle fiber and others?
it has a Plateau that lasts 0.2-0.3sec in ventricular muscle (much longer than other tissues)
325
What is the functional purpose of the plateau phase in cardiac muscle fibers?
To allow blood to be expelled/ventricles to empty
326
Closure of what ion channel causes the "spike" like drop at phase 1 of the Cardiac action potential?
Closure of fast Na channels- stops + from moving in
327
What two ions contribute to the the plateau phase in cardiac muscle fibers?
slow opening of calcium channels (phase 0)
closure of potassium channels (phase 1)
ca: + moving in
k: + moving out
plateau phase 2: k closes, ca opens, = more + inside, then k channels opens which allows lots of K to flow OUT = repolarization occurs
328
What ion initiates an action potential in cardiac muscle fibers?
Calcium
329
What occurs during each of the action potential phases of cardiac muscle fibers?
0: depolarization
1: early repolarization
2: plateau
3: repolarization
4: resting
330
What is the movement of sodium throughout the cardiac AP?
0: na channels open
1: na channels close
2: still closed
3: still closed
4: still closed
331
What is the movement of calcium throughout the cardiac AP?
0: ca channels copen
1: ca channels closed
2: ca channels open
3: ca channels close
4: remain closed
332
What is the movement of potassium throughout the cardiac AP?
0: k channels closed
1: k channels open
2: k channels close
3: k channels open
4: resting
333
How long is the plateau phase in ventricular cardiac muscle fibers?
0.2-0.3 sec
334
Why doesn't repolarization automatically occur when na channels close/k channels open in cardiac muscle tissue?
Because slow Ca channels open before the closure of Na channels to allow + charges to flow INTO the cell which prevents the cell from reaching the negative resting state.
335
What initiates repolarization to occur in cardiac muscle fibers?
K channels opening, doesn't cause repolarization due to open ca channels. ca channels must close for repolarization to occur
336
In cardiac muscle fibers _________ is initiated by na ch opening and ________ is initiated by k ch opening.
Depolarization, Repolarization
BUT ca channels must close for repolarization to complete/occur
337
During the _______ period, cardiac muscle cannot be re-excited UNLESS:
*absolute* refractory period because na channels are inactivated and k channels are slow to close
RP = about plateau period length.
PACs/PVCs can occur during *relative* refractory period
338
What is the difference between the absolute and relative refractory period?
absolute: when DEPOL/REPOL occurs (0 AP can occur regardless of amount of stimulus)
relative: when HYPERPOL occurs = why it needs ^^^ stimuli to initiate another depolarization
339
How long are refractory periods in the atria and ventricles?
A: 0.15 seconds
V: 0.25-0.30 seconds (only 0.05 sec is *relative*)
340
At what point in the depolarization phase of action potential in cardiac muscle fibers does na channel close? (bonus q: mV for skeletal m)
once membrane potential reaches +20mV, also stimulates ca channels to open around 0mV
Skeletal: 0mV
341
Why is it important to know the flow of ions throughout the cardiac cycle?
To assist in guiding treatment of alterations/arrythmias
342
What is the function of the T-tubule in cardiac muscle fibers?
It is much larger than that of skeletal muscle and stores much more calcium, which depends on extracellular calcium levels
343
_______ stores calcium in the T-tubules of cardiac muscle fibers, similarly to how _______ stores calcium in skeletal muscle.
mucopolysaccharides, calsequestrin
344
What stimulates calcium release for contraction to occur in cardiac muscle fibers?
Calcium released from the SR opens the ryanodine receptor (while in skeletal muscle DHP is attached to ryanodine to allow the release of calcium)
345
What structure is absolutely vital in allowing calcium to stimulate calcium to be released from the sarcoplasmic reticulum in cardiac muscle fibers?
T-tubule!!!!
346
What is the difference between the t-tubule of cardiac and skeletal muscle fibers?
Cardiac: larger and ^^^ calcium
347
Process of cardiac muscle contraction once calcium enters through T-tubule
1. Ca enters from extracellular fluid into t-tubule-into cell
2. Ca stimulates ryanodine receptor
3. calcium released from SR
4. same process of ca activating troponin/actin/myosin of skeletal muscle contraction
348
What allows cardiac muscle fiber relaxation after a contraction occurs?
There is a Ca-ATPase pump on the sarcoplasmic reticulum that uses ATP to take Ca OFF myosin head then stores it back into SR.
349
What occurs during Systole of the cardiac cycle?
ventricular muscle is stimulated by AP: contraction
350
What occurs during Diastole of the cardiac cycle?
ventricular muscle is reestablishing Na+/K+/Ca++ gradient and relaxing
351
The P wave of the EKG indicates:
Atrial contraction/depolarization
352
The QRS of the EKG indicates:
Ventricular contraction/depolarization
353
The T wave of the EKG indicates:
Ventricular repolarization/relaxation
354
Why isn't there a wave on the EKG that indicated atrial repolarization?
Technically, there is one... it's just buried under the QRS, which is higher voltage
355
Why is the LV the priority?
It's function directly influences cardiac output, whatever is in the RV is eventually going to end up in the LV either way
356
What initiates the entire cardiac cycle?
Atrial contraction (p wave)
357
Does ventricular filling rely totally on atrial contraction?
No, as blood fills atria, AV valves are open - this allows 80% of blood to move from the atria to the ventricles simply by gravity. The ventricles only depend on the atria for 20% of filling.
358
What is required for isovolumetric contraction to occur? How does this occur?
All valves must be closed.
ventricular volume ^; ^ pressure to close AVs, but not enough pressure to the pressure in the aorta
as contraction continues, SLs valves open, expels vent volume- relax once empty which opens AVs
359
What closes the AV valves?
pressure of the ventricles due to ^ volume
360
What opens the SL valves?
^^^^ pressure in the ventricles from both volume and contraction
361
What causes SL valves to close?
lack of volume = lack of pressure, causes blood in the aorta to begin flowing backwards and is then caught in the cusps of the valves which causes them to snap shut (dicrotic notch)
362
What causes the dicrotic notch?
closure of the SL valves: when the valves close, aortic pressure jumps up, due to the rapid increase of pressure (dilates great vessels) then levels out (rebound effect)
363
What causes the AV valves to open?
increased volume in atria/lack of in ventricles
364
What causes the heart sounds?
Lub: AV closure- S1
Dub: SL closure- S2
S3: dilated cardiomyopathy/^ volume (extra swish of volume in ventricle)
365
Isometric _____ occurs in Diastole while isometric ____ occurs in Systole.
Relaxation, Contraction
366
How is the ventricle still able to eject blood during the latter part of systole since LVP < AP?
The ventricular contraction creates Kinetic energy to drive the volume out regardless of the pressure gradient
367
What are the pressures of the chambers of the heart?
RA: 0-5
RV: 24-25
LA: 8-10
LV:130-140
R: deox/low p, L: oxy/high p
bonus: pap: 15-18mmHg
368
What factor heavily controls blood flow through the heart?
PRESSURE
369
What causes PAP to increase?
any kind of pulmonary pathology
thus increasing pressure in the right side of the heart which then must work harder to expel blood w/ higher pressure which causes development of cardiac hypertrophy
370
Why is CO measured over 1 minute?
because SV varies too much per stroke due to many factors
this, CO = HR x SV
371
How does the body compensate for changes in CO?
SNS/PNS alters SVR in response, which increase PRELOAD to the heart
372
how much blood typically fills the LV and how much is ejected?
170cc
Ejection fraction % out
LVEDV-LVESV = Stroke volume (SV)
373
What is a normal EF?
> 58%
374
How are athletes able to perfuse the body efficiently with a low heart rate?
High ejection fraction, more blood is pumped out per contraction
375
How is the heart able to alter CO based on demand?
SNS stimulation increases HR and contractility
376
What factors alter CO?
1. HR
2. SV
a. preload
b. afterloaf
c. contractility
377
What is afterload?
volume that remains in LV after contraction or LVESV (^ vol left, less got out)
bc many factors contribute to EF such as SVR, preload, contractility
378
Afterload is ________ _________ to Cardiac output.
inversely proportionate
379
How does aortic stenosis (AS) alter Cardiac Output?
applies resistance to LV, depressing function leading to a decreased cardiac output
380
How does distributive shock (low SVR) alter CO?
low SVR decreases resistance, so LVESV would be low/CO would be high but low SVR decrease preload which causes a decreased CO
381
What is stated by frank starling law?
Increased blood volume (vasodialation ^ blood volume/preload), filling increases contractility which ^^^ CO
382
Parasympathetic/Vagal nerve fibers mainly intervate the:
atria, slow HR
383
How does SNS/tachycardia decrease CO?
decreases Ventricular filling
