Exam 1 Flashcards
(166 cards)
1
Q
What is an electrical synapse and how is it different from a chemical synapse?
A
In electric synaptic transmission, IONIC CURRENT flows PASSIVELY by diffusion through A PAIR OF GAP JUNCTIONS from presynaptic terminal to post synaptic membrane and directly alter the membrane potential.
VERY RAPID/ CLOSE (few nm) COMMUNICATION
NOT COMPLEX/FLEXIBLE
UNCOMMON in mammalian nervous system
In Chemical synapse, MORE COMMON in mammalian nervous system USE NEUROTRANSMITTERS NO GAP JUNCTION channels Have structural specialization - synaptic vesicles, pre/post synaptic densities LARGER GAP of communication (20-40nm)
2
Q
How do you determine change in membrane potential for electrical synapse and what directions can electrical synapse go?
A
Change in V (membrane potential) = I · Rm
SOME electrical synapse - ONE DIRECTION (rectifying- sense voltage differences)- open only when presynaptic terminal is depolarized
MANY electrical synapse - BI-DIRECTIONAL (not-voltage sensitive)
3
Q
What type of synapse do not allow for much complexity or flexibility in cell to cell communication? Why?
A
ELECTRICAL SYNAPSE
They do not provide a mechanism for inhibitory synaptic communication
4
Q
What are the structural features of chemical synapse and their specific functions ?
A
MITOCHONDRIA - high rate of use of metabolic energy in presynaptic terminal
SYNAPTIC VESICLES- round, sub-cellular organelles found in presynaptic terminal (has many neurotransmitters). Membrane composed of lipid bilateral and integral proteins and transporters
PRE synaptic densities - cluster of proteins where neurotransmitter is released (tethered to filaments which extend from membrane to cytoplasm of presynaptic terminal).
POST synaptic density- neurotransmitter receptors, G-proteins, enzymes, structural proteins
ECM/Basement membrane- at synaptic cleft between pre and postsynaptic plasma membrane. Has AchE that breakdown acetylcholine
5
Q
The synaptic vesicles in a presynaptic terminal of chemical synapse has a vesicle membrane that contains —
A
Primary active transporter (H+ -ATPase) - concentrates proton within the vesicle
Proton gradient is used to energize specific neurotransmitter carrier protein ( secondary active transporter)- loads the vesicle with the neurotransmitter
6
Q
Chemical synapses are found at what 3 different locations on the postsynaptic neuron
A
axo-dendritic synapses (Shifts and spines)
Axo-somatic synapse (cell body and axon hillock)
Ayo-axonic synapse (pre-synaptic terminal of axon)
7
Q
What vesicle membrane protein is responsible for mobilization of synaptic vesicles from being bound to cytoskeleton filaments to their release into the active zone of presynaptic terminal? What state is the protein in?
A
Synapsid
Phosphorylated state (by PKA and CaMK)
8
Q
Synapsin have high affinity for actin filaments in what sate? Result in what?
low affinity in what state ? Result in what?
A
High affinity in dephosphorylated state - vesicles for a reserve pool
Synapsin has low affinity for actin filaments in phosphorylated state - result in releasable pool of vesicles mobilized to active zone.
9
Q
What determines neurotransmitter release ?
A
High conc of Ca2+ by influx/inward flow
Increased Ca levels - CaMK activated - synapsin phosphorylated - vesicles mobilized from actin cytoskeleton
10
Q
Name 2 reasons why docking and priming important? What step should this be? What proteins help with this?
A
1) To position a vesicle at active zone in presynaptic terminal where VGCa channels are located. This reduce delay btw entry of calcium into terminal and elease of neurotransmitter
2) To position vesicle adjacent of plasma membrane. This enables fusion and exocytosis to occur.
Should be first step before mobilization
VSNARE - synaptobrevin
TSNARE - SNAP 25 and syntaxin
soluble/cytoplasmic proteins - regulate snare complex assembly and disassembly
11
Q
What calcium sensor helps with fusion by influx of Ca binding to it? What happens to this calcium sensor after?
A
Synaptotgmin
Calcium binding to synaptotagmin increases its lipid solubility which enable synaptotagmin to move into plasma membrane and fuse with the vesicle membrane (stimulate fusion and exocytosis)
12
Q
2 types of exocytosis/fusion
A
Kiss and run fusion - fusion pore open briefly and allow vesicle empty its contents (neurotransmitter) into the synaptic cleft but then close after.
Complete fusion- Fusion pore dilate rapidly and completely leading to complete fusion of vesicle and plasma membrane and release of neurotransmitter into the synaptic cleft
13
Q
What toxins affect neurotransmitter release?
A
Tetanus toxin - cleave docking and priming proteins and will prevent neurotransmitter release. Active in axon terminal of inhibitory spinal interneurons. Uncontrolled muscle contractions and spasms - start in JAW
Botulism toxin - (active in axon terminal of motor neurons) cleave docking and priming (SNARE) protein, prevent release of Ach to NMJ- cause paralysis, respiratory paralysis in extreme conditions
Animal toxin - Black widow spider has alpha Latrotoxin - axon terminal membrane- stimulate massive release of neurotransmitter - constant painful muscle contractions and cramps
Cone snails - conotoxin- loss of voltage gated calcium channel- failure of neurotransmitter release
14
Q
Diffusion of neurotransmitter out of synaptic cleft is a slow way to terminate neurotransmitter action? What are faster ways and how does it work?
A
Re-uptake - High affinity transporter proteins (specific re-uptake carriers and glial cells) - use secondary active transport -sodium dependent cotransport
Degradation - Enzymatic degradation. Eg extracellular enzyme AchE found in synaptic cleft and hydrolysis ACh to choline and acetate
15
Q
Clathrin and dynamic are used to recycle vesicle membranes by refilling neurotransmitter and returned to reserve pool o release pool. This process is called
A
Endocytosis
16
Q
Differentiate between small and large neurotransmitters
A
SMALL NTs
Low MW,
E.g A.A (Glutamate, GABA), Ach, Biogenic amines (NE), Purines (ATP)
Synthesized and packaged into vesicles within the cytoplasm of NERVE TERMINAL
LARGE NTs
High MW
Neuroactive peptides
Synthesized and packaged into vesicles within the CELL BODY
17
Q
Which small neurotransmitter is used at the neuromuscular junction? which is used at the ANS (by pre and para postganglionic neurons) and by brain neurons ?
Synthesized by what enzyme?
Precursors for synthesis?
A
ACh- Acetylcholine
Choline acetyl transferase (ChAT)
Precursors are CHOLINE (from blood) and ACETYL CoA
18
Q
3 biogenic amines are catecholamines, serotonin and histamine.
What is pathway of catecholamine synthesis? What is the parent precursor ? Enzymes?
A
Parent precursor of catecholamines is TYROSINE
Tyrosine - dopa (tyrosine hydroxylase)
Dopa- dopamine (Dopa decarboxylase)
Dopamine - norepinephrine (Dopamine beta hydroxylase)
Norepinephrine - epinephrine (PNMT- methyl transferase)
Dopamine (expressed in substantia Nigra and ventral tegment - project in striatum, amyygdala and frontal cortex
NE - locus ceruleus CNS
Epinephrine- Adrenal medulla (express all enzymes)
19
Q
3 biogenic amines are catecholamines, serotonin and histamine.
What is the precursor for serotonin synthesis ?
Enzyme?
Where are serotonergic neurons found?
A
TRYPTOPHAN - 5-HTP (Tryptophan hydroxylase)
5-HTP - Sertonin (5HT) by 5-HTP decarboxylase
2 step process
Serotonergic neuron found in raphe nuclei of brain stem- axons project to CNS
20
Q
3 biogenic amines are catecholamines, serotonin and histamine
What is the precursor of histamine?
What enzyme?
Functions?
A
Histidine - Histamine (Histidine decarboxylase)
Synthesized n some neurons of the hypothalamus
Function as neurotransmitter and signaling molecule
21
Q
3 A.A used as neurotransmitters are glycine, glutamate and GABA.
What are their roles? Inhibitory vs excitatory and what pat of body?
Precursor and enzyme of GABA synthesis?
A
Glycine- main inhibitory NT in spinal cord
Glutamate - main excitatory NT in CNS
GABA- main inhibitory NT in brain.
Glutamate - GABA ( glutamic acid decarboxylase)
22
Q
ATP (a small NT) is degraded into what by ecto-nucleotides? This product can them accumulate into the extracellular space as a result of intracellular ATP hydrolysis. What is the function of this product?
A
Adenosine.
Extracellular adenosine is a signaling molecule that alter neuronal function
23
Q
Small NT Nitric Oxide (NO) is synthesized by what?
Enzyme?
Is NO stored in vesicles? Why/Why not?
What is the target/receptor of NO
A
NOS- calcium - Calmodulin dependent
NO is not stored in vesicles because it is a gas and can diffuse out of the cell . It Is produced when calcium flows into the axon terminal during A.P
Receptor is soluble/cytotoxic guanylyl Cyclase - stimulate GTP- cGMP - activate PKG protein kinase - phosphorylated synapsin.
24
Q
Differentiate between ionotropic and metabotropic receptors
A
IONOTROPIC/ DIRECT receptors Receptor DIRECTLY gates an ion channel MORE RAPID synaptic transmission Exist for many small molecule transmitters like Ach, glutamate, glycine Has modulating site for other functions
METABOTROPIC/ INDIRECT G-protein coupled receptors
Receptor indirectly regulates an effector molecule which could be ion channel or enzyme through a G protein.
Postsynaptic potentials are SLOWER
Affect ENZYME ACTIVITY (Adenylyl cyclase and PLC) in addition to ion channel
25
```
WHat are the basic receptor types and mechanism for
Ach - ACETYLCHOLINE
Glutamate
GABA (a and b)
Glycine
```
ACETYLCHOLINE
Nicotinic -(ionotropic receptor) -directly open cation channels (Na and K)
Muscarinic (metabotropic M1,M3,M5) - stimulate PLC, close K channels
Muscarinic (metabotropic M2, M4)- inhibit Adenylyl Cyclase, open K channels, inhibit Ca channel opening
26
```
WHat are the basic receptor types and mechanism for
Ach
GLUTAMATE
GABA (a and b)
Glycine
```
```
GLUTAMATE
Ionotropic receptors (KA,AMPA, NMDA) - directly open cation channels (Na/K or Na/K/Ca)
```
Group 1 metabotropic - stimulate PLC
Group 2 and 3 metabotropic - inhibit AC
27
```
WHat are the basic receptor types and mechanism for
Ach
Glutamate
GABA (a and b)- GABA a/b
Glycine
```
GABA A
Ionotropic
Directly open CL- channels
GABA B
Metabotropic
Open K+ channels, inhibit Ca2+ channel opening
28
```
WHat are the basic receptor types and mechanism for
Ach
Glutamate
GABA (a and b)
GLYCINE
```
GLYCINE
GlyR; Ionotropic
Directly open Cl- channels
29
The post synaptic response that increase the probability of action potential firing in pot synaptic neuron is called —
Excitatory postsynaptic potential (EPSP)
Depolarize the postsynaptic cel membrane potential towards the threats hold for opening of voltage gated Na+ channels
30
The change in the postsynaptic ion permeability that DECREASES the probability of action potential firing is called —
Inhibitory postsynaptic potential (IPSP)
Synaptic current flow hyperpolarize the postsynaptic membrane. IPSP can also result from ion permeability changes that reduce ability of cell to reach threshold
31
How do ionotropic receptors permeable to both Na+ and K+ generate conductance increase EPSPs
The driving force is 5-6times greater for Na+ thank K+ .
Inward Na+ current is several times greater than outward K+ current. This will DEPOLARIZE the neuron.
For depolarization to be excitatory, the equilibrium potential for current flow must drive AP to threshold i.e toward positive. In this case it is -1 (close to 0mV)
32
What are common ionotropic receptor types that mediate conductance increase EPSPs.
Where are they found?
Nicotine Ach receptors - found at NMJ (initiate muscle A.P which cause muscle contraction), also found in ANS and some synapses in CNS
Ionotropic glutamate receptors - tetramers found at excitatory synapses of brain (marinate, AMPA, NMDA)
***NMDA is permeable to Ca2+ in addition to Na, and K.
33
The amplitude and direction of the total synaptic current (Isyn) depends on what 2 factors
The NET DRIVING FORCE (difference btw cell membrane potential and synaptic equilibrium potential)
SYNAPTIC CONDUCTANCE (gsyn- directly proportional to the number of open channels)
Isyn = (Vm - Esyn) · gsyn
34
Synaptic potential Vsyn is dependent of 2 factors?
Vsyn = Isyn · Rm
SYNAPTIC CURRENT
And
RESISTANCE of cell membrane
35
The lag between the peak of the synaptic current and the peak of the synaptic potential is due to what?
Membrane time constant
| Measure of the amount of time required to rearrange the charge in the cell membrane
36
How do metabotropic (e.g muscarinic Ach) receptors which decrease resting K+ channels generate conductance decrease EPSPs?
By decreasing the resting leak potassium permeability (normally the leak channels are open and contribute to negative resting membrane potential). This removes the hyperpolarizing influence allowing the membrane potential to depolarize.
37
How do metabotropic receptors which increase the resting K+ conductance generate conductance INCREASES IPSPs. (2 ways)
INDIRECT GATING OF K+ CHANNELS
E.g GABA b and muscarinic Ach receptors.
Activate G-protein which In turn open K+ channels which hyperpolarize the neuron lead to postsynaptic neuron INHIBITION
DIRECT GATING OF Cl- CHANNELS
E.g Glycine and GABA A receptors (multimeric)
Cause opening of the Cl- permeable ion channels which will stabilize the membrane potential and reduce ability of cell to depolarize. (Equilibrium potential of Cl must be less/negative to action potential threshold)
38
How does ionotropic receptors permeable to Cl- generate conductance increase IPSPs
As long as ECl is negative to the action potential threshold, a postsynaptic response generated by glycine or GABA a receptors will be inhibitory.
39
How does conductance decrease IPSPs
Closure of cation permeable leak channels
Very UNCOMMON
40
How does LENGTH constant affect dendritic integration through SPATIAL summation
Many neurons of CNS e.g pyramidal cell has large dendritic tree and short length constant. For this, there has to be simultaneous activation of SEVERAL excitatory synapses in order to depolarize the axon to threshold.
The LENGTH CONSTANT determines the the degree to their is SPATIAL SUMMATION to create action potential .
41
How does TIME constant affect dendritic integration through TEMPORAL summation
The time constant of a neuron determines the speed with which a synaptic current can change the postsynaptic membrane potential.
Short time constant- allow membrane potential to change rapidly but can cause potential to decay back to resting level once current stop flowing
Long time constant - membrane potential not changing rapidly but can persist for a longer period even after the flow of current ends
In temporal summation, same synapse is activated more than once with short period of time, DEGREE OF TEMPORAL SUMMATION DEPEND ON TIME CONSTANT
42
What happens when both the excitatory and inhibitory synapses are simultaneously active
EPSP and IPSP will add together to affect the membrane potential at the axon
If 2 synaptic potentials are equal and opposite = NO CHANGE in membrane potential will occur.
Neuron will only fire an A.P when the result of the spatial and temporal integration depolarize the axon to threshold
43
Distant synapse from the axon will have what effect compared to the proximal synapse
Weaker
44
Presynaptic receptors found on presynaptic axon terminal membrane.
Name the synapses?
Effect of the synapses to neurotransmitter release?
Which effect is more common? What mechanisms/receptors?
Axo-axonic synapses
Facilitate or Inhibit neurotransmitter release.
Inhibition is more common - involves metabotropic GPCR. Which either :
Open K+ channels or inhibit Ca2+ channels from opening
45
How do autoreceptors of presynaptic receptors function?
They are similar to the inhibitory presynaptic receptors but do not require an axo-axonic synapse. Instead, they are activated by transmitter released from their own terminal.
Negative feedback - Inhibit the release of neurotransmitter
46
Numerous proteins inside cell can be substrates for protein kinases ad neurotransmitter- stimulated phosphorylation of these proteins can alter cell function but cause NO CHANGE to membrane potential. This type of alteration is called —
Neuromodulation
47
Spillover of neurotransmitters like NO to non-synaptic extracellular space result in swelling/varicosities. Release of the ranks titer has a diffuse effect on many different cells. This type of signaling is called —
Volume transmission
48
In infancy (0-1 year) Which senses is the most developed? Which is the least developed?
Touch
| Vision
49
Social smile develop by what age
1-2 months
50
When do children begin toilet training? When do they have it mastered?
Begin at toddlerhood (1-3)
| Mastered by Pre-school (3-6 yrs)
51
Conservation is mastered at what stage of development
School age (6-11 yrs)
52
The vertebral column is the core of the body. Name 4 important functions of the vertebral column?
1) SUPPORT BODY WEIGHT - transmit weight to pelvis and lower limb
2) HOUSES AND PROTECTS SPINAL CORD- spinal nerves leave cord btw vertebrae
3) PERMITS MOVEMENT - clinical problems can result from this - back/spine problems
4) PROVIDES FOR MUSCLE ATTACHMENT- muscles of back, head, neck, upper extremity, thorax.
53
What is the second most common cause of disability? What function of vertebral column is responsible for this? What is the first cause of disability?
Back and spine problems is second cause of disability
Vertebral column permits movement
Arthritis is first cause of disability
54
Match the anatomical positions
1) toward midline
2) away from midline
3) front of body (2 names)
4) Back of body (2 names)
5) toward top of head (2 names)
6) toward bottom of feet (2)
1) Medial
2) Lateral
3) Anterior/ventral (NOSE IS ANTERIOR)
4) Posterior/Dorsal
5) Superior/Rostral
6) Inferior/caudal
55
Name the anatomical positions
7) closer to trunk or origin of structure
8) away from trunk
9) palm side (2)
10) back side of hand
11) top of foot
12) sole of foot
7) Proximal
8) Distal
9) Palmar/ volar surface
10) Dorsal surface of hand
11) Dorsal side of foot
12) Plantar surface of foot
56
Match the 3 anatomical planes
1) Divides the body in RIGHT and LEFT parts? Right and left halves
2) Transverse plane/ Cross section - divides body into TOP and BOTTOM parts perpendicular to long axis of body
3) Divides body into FRONT and BACK parts
1) SAGITTAL PLANE /Median SAGITTAL Plane
2) HORIZONTAL PLANE
3) CORONAL PLANE
57
Spinal nerves leave vertebral canal via —
INTERVETEBRAL FORAMINA - btw pedicles of vertebral arch bordered by superior and inferior vertebral notches
58
5 parts of a typical vertebra (thoracic by convention)
1) Body (anterior position, transmits body weight)
2) Vertebral arch - pedicles and lamina
3) Spinous and Transverse processes (posterior and lateral projections from arch for muscle and ligament attachment)
4) Intervertebral foremen (spinal nerves leave vertebral canal from here)
5) Superior and Inferior articulation process/facets (orientation determines movement btw vertebra)
59
5 regions of Vertebral column and the location and number of vertebra for each.
1) CERVICAL (neck) 7 vertebrae C1-C7
2) THORACIC (Chest) 12 V. T1-T12
3) LUMBAR (lower back) 5. V L1-L5
4) SACRAL (pelvis) 5 fused vertebrae S1-S5
5) Coccygeal (Tail) 3-5 V. Co1-Co3
60
```
Name the vertebral type
Has
Foramen Transversarium
Bifid/divided spinous processes
Articulate facets angles superiorly and medically (for flex-extend, lateral flex and rotate movements)
Small bodies
Most mobile
```
CERVICAL VERTEBRA
61
Different between C1 (Atlas), C2 (Axis) and C7 of Cervical Vertebra
C1- Atlas
- No body/only ring of bone
- Anterior and posterior arch with bumps (tubercles)
- Superior articulate facet- flex-ext (head nod/say YES)
C2- Axis
Odontoid process/DENS
PIVOT joint -rotation- say NO- hanging
C7- Vertebra prominens
Small foramina transversaria
Spinous process -long NOT BIFID - PALPABLE
62
Which cervical vertebra transmit only vertebral veins and not artery? Why? Which transmit artery?
C7- vertebra prominens
Has small foramina transversaria
C1-C6- transmit vertebra artery
63
Name the vertebrae
-BODY- Heart shaped
-COSTAL FACETS for ribs on - body (facet for heads of ribs) and Transverse process (facet for articulate tubercles of ribs)
-Spines of thoracic vertebra -long and inclined posterior and inferior
-CORONAL PLANE- Articular process oriented here
-Articular process in coronal plane cause NO FLEX, EXTEND, SMALL ROTATION
LEAST MOBILE (House heart and lungs)
THORACIC VERTEBRA
64
Name the vertebrae
- HEFTY/LARGE body
- Stout pedicles, thick lamina, broad spinous process
- Articular process in SAGITTAL PLANE
- can FLEX-EXTEND , NO ROTATION
- help you tie you shoes
LUMBAR VERTEBRA
65
Name the vertebra
-5 fused Vertebra
-Anterior and posterior sacral foramina - intervetebral foramina
-Medial crest- fused spinous process
Sacro-lliac joint- transmit weight from vertebrae to pelvis (innominate bone)
-NORMALLY NO MOVEMENT
SACRUM/ SACRAL VERTEBRA
66
Name the Vertebra
3-5 fused vertebrae
RUDIMENTARY TAIL BONES
NO MOVEMENT
COCCYX
| Coccygeal vertebra
67
Name the Ligament
- join anterior side of bodies of vertebrae
- Broad and STRONG band
- prevents disc herniation anteriorly
ANTERIOR Longitudinal LIGAMENT
68
Name the ligament
- on posterior side of bodies of vertebrae (Inside vertebral canal)
- WEAKER/ NARROW band
- Disc herniate LATERAL to ligament
POSTERIOR Longitudinal LIGAMENT
69
Name the ligament
- yellow elastic bands connecting LAMINAE OF VERTEBRAE
- allows for movement of vertebrae
- LAST LAYER penetrated by needle in epidural anesthesia
LIGAMENTA FLAVA
70
Name the Ligament
- connects SPINES OF VERTEBRA
Greatly thickened in cervical/neck region to form LIGAMENTUM NUCHAE- from ext. occipital protuberance of skull to C7
-support head, provide muscle attachments
INTERSPINOUS and SUPRASPINOUS ligaments
71
SUMMARY of location of 4 ligaments
- Anterior longitudinal - anterior side of bodies
- Posterior longitudinal- posterior side of bodies/inside canal
- LIGAMENTA flava - laminae of vertebrae
- INTERSPINOUS and supraspinous ligament- spines of vertebrae (spinous process area)
72
`What are the 2 joints between vertebra
1) Joints between Articular Processes (facets) - SYNOVIAL plane joints that permit sliding movement; IMMOBILIZED in facet fusion surgery
2) Intervertebral discs- interposed btw bodies of adjacent vertebrae, each disc consist of NUCLEUS PULPOSUS (inner gelatinous part) surrounded by ANULUS FIBROSUS (collagenous fibers and fibrocartilage)
73
What are the components f synovial joints and how is it lubricated?
Synovial joints of btw Articular processes have a connective tissue capsule and synovial fluid inside the capsule. The fluid minimizes friction ad lubricates the joint
74
A 45 year old nurse comes in complaining of painful nerve compression. She stated she strained her back at work. Scan shows a DISC displacement with a bulge in posterolateral direction.
What is the diagnoses?
What is bulging out?
What is the direction of the bulge?
HERNIATION OF NUCLEUS PULPOSUS - Slipped disc
Nucleus PULPOSUS (inner gelatinous core) bulge out lateral to posterior longitudinal ligament (inside canal)
Often in L4-L5 or L5-S1
Can lead to NERVE COMPRESSION of intervetebral foramen
75
What are the normal spinal curvatures for primary, secondary and lateral curvatures?
PRIMARY- Concave ANTERIORLY(All of vertebral column, retained in the thoracic and sacral regions with age)
SECONDARY- Cervical (hold up head) and Lumbar (support body, develops with walking) regions concave POSTERIORLY
LATERAL- concave AWAY from handed ness (mainly cervical and lumbar)- help in lifting heavy objects by shifting center of gravity
76
Name the abnormal curvature
- Exaggerated curvature concave anteriorly
- usually in thorax of elderly
- HUMP back
- due to OSTEOPOROSIS
KYPHOSIS
77
Name the abnormal curvature
- Exaggerated lateral curvature
- KINK in spine
- thoracic, LUMBAR most common
- due to HEMIVERTIBRA (half of vertebral body (T3) does not form)
SCOLIOSIS
78
Name the abnormal curvature
- Exaggerated lumbar curvature
- Large Concave POSTERIORLY
- Lumbar - normal in PREGNANCY
- abnormal cause is OBESITY
LORDOSIS
79
The ligament nuchae in the cervical region represents a specialization and thickening of —
SUPRASPINOUS and INTERSPINOUS ligaments
80
Group of cell bodies in CNS is called ?
Group os axons in CNS?
NUCLEI
TRACTS
81
Group of cell bodies in PNS is called ?
Group of axons in PNS called?
GANGLION (except dorsal root ganglion)
NERVES
82
What is the STRUCTURAL classification of the nervous system
CNS (Central NS)
- Brain (in cranial cavity)
- Spinal cord (in vertebra canal)
PNS (Peripheral NS)
- Everything else
- Nerves (cranial and spinal nerves- carry signal from CNS)
- Ganglia (collection of nerve cell bodies)
- Sense organs (eye, inner ear etc)
83
What is the FUNCTIONAL classification of the nervous system
SOMATIC NS
- conscious/voluntary
- Somatic EFFERENT- control SKELETAL muscle, voluntary activity and movement
- Somatic AFFERENT- sensory neurons that innervate skin, joints; provide PRECISE conscious sensation of touch pressure , pain and sense of body position
AUTONOMIC NS
-automatic, unconscious, Visceral
-Visceral EFFERENT (Para and sympathetic)- control SMOOTH muscle, unconscious actions
Visceral AFFERENT- sensory neurons that innervate internal organs, IMPRECISE location of sensation
84
Classification and number of cranial and spinal nerves
CRANIAL
- 12 nerves
- arise from/project to brain
SPINAL
- 31 nerves
- 8 Cervical nerves
- 12 thoracic nerves
- 5 lumbar nerves
- 5 sacral nerves
- 1 coccygeal nerve
85
What contains cell bodies of all sensory neurons (somatic and visceral) ?
What side of spinal nerve is this located?
Dorsal root ganglia
Dorsal side (afferent)
86
How are levels of spinal nerves oriented?
C1-C7 is above the vertebrae
C8 downwards is below the vertebrae
87
An area of skin innervated by a single spinal or cranial never is called —
Overlap is greatest where ?
Why is this clinically important?
DERMATOME
Trunk
can test for damage to specific nerve by lightly touching (pin prick) area of skin in dermatome (will have pain or numbness/anesthesia)
88
What are the important dermatomes of upper and lower extremity?
UPPER EXTREMITY
C6- Thumb
C7- middle finger
C8- little finger
LOWER EXTREMITY
L1- region of lnguinal ligament
L4- Big toe
S1- Little toe
89
Development of spinal nerve
How does plexus give rise to nerves ?
Ventral and dorsal rootlet - ventral and dorsal root- SPINAL NERVE - ventral and dorsal rami
Ventral rami- form plexus (complex braid like nerves with sensory and motor axons) -
1) cervical plexus- innervates neck
2) Brachial plexus- innervates upper extremity from C5-T1 of ventral rami
3) Lumbosacral plexus- innervates lower extremity , from L1-S4
Each plexus gives rise to nerves E.g sciatic nerve is from L4,5 and S 1,2,3 of ventral rami
90
The CONUS MEDULLARIS is the inferior/caudal/bottom end of the spinal cord. It is located differently in newborn and adults.
What are the reps. Locations?
Why different?
Newborn- conus medullaris is at L3
Adult - conus medullaris is at L1
During development, spinal column increases greatly in length compared to spinal cord which only has small increase
91
During development, as the spinal column grows longer, the LOWER DORSAL and VENTRAL ROOTLETS also grow longer and go through the intervetebral foramen and extend to the lower lumbar, sacral and coccygeal levels. These rootlets are collectively called —
CAUDA EQUINA/ Horse tail
92
What are the connective tissue layers that surround and protect the spinal cord?
Identify and state the function
Collective name
3 layers
2 space
MENINGES
```
3 layers
DURA MATER (tough mother)
ARACHNOID MATER (spider like)
PIA MATER (tender mother)
```
2 spaces
Epidural Space
Subarachnoid space
93
Tough outer layer of meninges that forms sac, completely surrounds the spinal cord in vertebral canal
-below L1 in adult, below L3 in newborn
Function?
DURA MATER
| Forms dural sac that surround the cauda equina, dural sac ends inferiorly at level S2
94
Dural sac formed from dural mater is separated from inner side of vertebral canal by what space?
What does space contain?
EPIDURAL SPACE
Contains
- fat and loose connective tissue
- INTERNAL VERTEBRAL VENOUS PLEXUS (collection of veins)
*** Epidural Anesthesia- block conduction of spinal nerve, injection into epidural space
95
Middle layer of meninges, ATTACHED TO INNER SIDE OF DURA
ARACHNOID MATER
| has fine strands that extend to pia mater (spider web like
96
What space is found between arachnoid and pia ? What does it contain?
SUBARACHNOID SPACE
CSF - cerebrospinal fluid
97
What is pia mater? What does it contain?
- Thin layer adherent to surface of spinal cord
- contains blood vessels that supply cord
1) Denticulate ligaments - landmarks for surgery (btw the dorsal and ventral rootlets of spinal nerves)
2) Filum termnale (formed of pia mater, attaches inferiorly at Co1)
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What is CSF?
Function?
Where is it produced ?
Abnormal changes in CSF like over production lead to what?
- CSF is clear acellular fluid contained in the subarachnoid space
- surrounds and protects spinal cord
- produced within CHOROID PLEXUS/mostly in brain
- excess CSF lead to HYDROCEPHALUS - increased pressure
- blood cells in CSF can also indicate INFECTION or HEMORRHAGE)
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CSF can be sampled by INSERTING NEEDLE INTO SUBARACHNOID SPACE
What is procedure called?
Position?
Level in newborn and adult?
LUMBAR PUNCTURE or spinal tap
Vertebral column flexed and patient sitting or lying on side (lateral decubitus position)
Newborn - L4 - L5 (Spinal cord extends to L3)
Adult - L3-L4 or L4-L5 (spinal cord extends to L1)
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What must needle pass through to enter subarachnoid space in lumbar puncture?
What are the 2 pop
1) Skin
2) superficial fascia
3) supraspinous ligament
4) Interspinous ligament
5) LIGAMENTUM FLAVUM - first pop
6) Epidural space (CT and fat)
7) DURA MATER- second pop
8) Arachnoid
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Structure of NMJ
| 5 components
1) 1 Motor neuron innervates 1 group of muscle fibers -motor unit. Axon makes single contact with fiber at NMJ or end plate
2) Presynaptic nerve - has Ach neurotransmitter
3) Postsynaptic cell - post junctional folds
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How is action potential generated when Ach binds to its receptor?
- Motor neuron A.P
- Ca2+ enters voltage gated channels
- Motor neuron release Ach - bind to Achreceptors on muscle membrane
- Allow Na+ to enter cell and little K+ exit (cause postsynaptic membrane potential to DEPOLARIZE)
- In turn activate VGNa+ channels which lead to propagation of ACTION POTENTIAL in muscle plasma membrane
- Ach degraded by AchE
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When 2 Ach molecules binds to receptor, channel briefly opens and entrance of sodium ions cause a current called —
End plate current (EPC)
Cause voltage tp become more positive at end-plate
-change in potential (EPP- end plate potential) lead to postsynaptic action potential
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When presynaptic motor neuron is not simulated, what changes can be seen in MUSCLE membrane potential?
MEPPs - miniature end plate potentials
Looks like EPPs but are much smaller in AMPLITUDE
Caused by spontaneous release of QUANTA of Ach
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What is the difference btw actual EPP and threshold potential required to generate muscle action potential ?
What will reduce the EPP? What is the effect on action potential?
Safety factor
Repetitive stimulation of nerve
Will NOT prevent action potentials
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Structure of Ach receptor
How many subunits?
Types in mammals
Nicotinic AchR- because nicotine binds to receptor
5 subunits
Embryonic and Adult receptors
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Which type of Ach receptor has LONGER single single channel mean OPEN TIME and LOWER single channel CURRENT
Embryonic receptor
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Which Ach receptor type has SHORTER single channel mean OPEN TIME and GREATER single channel CURRENT
Adult receptor
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What is required for the initiation of NMJ formation and for assembling other proteins at NMJ?
What are the steps of NMJ formation?
MuSK (muscle -specific kinase) is required
A. Motor neuron release Ach before making contact with muscle target
B. Muscle membrane can respond to Ach before contact with neuron
C. Motor neuron contact muscle membrane and AMPLITUDE of EPP INCREASES
D. Structure of presynaptic nerve and postsynaptic muscle change (AchR aggregation move from center of muscle fiber to when fiber and neuron come in contact). INCREASE cluster of receptors
E. Existing receptors are clustered by AGRIN (released from nerve)
F- AGRIN activate MuSK which induce further cluster by RAPSYN
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WHat bind to AGRIN and MuSK
LRP4
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WHat regulates interaction of MuSK and LRP4
AGRIN
112
What activates MuSK?
What is required?
AGRIN
Muscle protein Dok-7 required
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What happens with appearenance of AcHR clusters at NMJ
Extrasynaptic clusters disappear
| Balance between clustering and dispersal of AcHR
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WHat causes dispersal of AchReceptrs
What counters this?
Ach - acetylcholine (prevents extrasynatic clustering of receptors)
AGRIN counterbalance this at NMJ
Ach and AGRIN required for the balance btw clustering and dispersal of acetylcholine receptors
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In adult synapses, channels with what will help maintain stimulus-response relationships btw firing of motor neuron and muscle contraction?
Short open times
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Early in development of NMJ, 1 muscle fiber is innervated by how many motor neuron?
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What reduces this number ?
What regulates this?
WHat is secreted?
End result of eliminated motor neuron?
What happens if muscle is enervated?
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- Multiple motor neurons —Synapse elimination leaves one remaining
- Regulated by ELECTRICAL ACTIVITY btw nerve and muscle
- Involve SECRETION of tropic factors and AchR
- synaptic strength of input neuron decreases, loss of receptors,
- presynaptic terminal eventually withdraws
- is muscle denervated, regenerating motor neurons will reinnervate at original site
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What toxin blocks the release of Ach
BOTULINUM toxin
| Tetanus toxin
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WHat drug activate AchR? What else?
What toxin inhibit AchR?
Activated by NICOTINE
Acetylcholine
Inhibited by CURARE (d-tubocurarine) and SNAKE VENOM (alpha-bungarotoxin)
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What drugs inhibit AchE- Acetylcholinesterase ?
What will buildup if AchE is inhibited?
Physostigmine and neostigmine
If AchE inhibited, Ach build up. (Decreased levels of acetate and choline)
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What toxin blocks MUSCLE and NEURONAL Na+ channels?
TETRODOTOXIN
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What does conotoxin do?
Example of conotoxin?
Peptides produced by fish-hunting MARINE CORE SNAILS
Blocks NEURONAL Ca2+ channels, MUSCLE Na+ channels and AchR
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Diseases that affect NMJ?
Myasthenia gravis
Lambert-Eaton syndrome
Congenital myasthenia syndrome
Botulism
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Name the disease
Most patients have antibodies against AchRs
Some patients have antibodies to MuSK
Patients have much REDUCED AchR levels at NMJ and degeneration of post junctional folds
S&S- weakness and fatigue, WORSE with EXERTION/EXERCISE, ocular muscle weakness
DROOPY eyelid- ptosis
MYASTHENIA GRAVIS
(Decreased AchR, EPP and MEPPs smaller than normal, No contraction)
Tx
AchE inhibitors- edrophonium
Drugs that REDUCE immune response
Removal of AchR antibodies
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Name the disease
- Make antibodies against PRESYNAPTIC Ca2+ channels
- reduction in neurotransmitter release
- EXERCISE IMPROVES weakness
S&S
Decreased Ach
Skeletal muscle weakness
Affect limb muscles primarily
LAMBERT-EATON syndrome
LUNG cancer pt
Tx
EXERCISE to increase Ach
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Congenital myasthenia syndromes affects what an why?
```
AchRs
Dok-7
MuSK
rapsyn
LRP4
```
These help to form NMJ
S&S -muscle weakness/myasthenia
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Name the disease
- Affects autonomic nervous system as well as NMJ
- inhibits synaptic vesicle release (prevent fusion of vesicle to membrane)
S&S- weakness and limbs paralysis
Death from respiratory muscle paralysis
Botulism
Caused by botulinum toxin from Clostridium botulinum
Tx
Toxin - to muscle contracture, spasms, strabismus (cross-eyes), headaches
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How does aging affect NMJ?
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Decreased muscle function
Synaptic area decreases
Number of post-synaptic folds decrease
Lose motor nerves
Reinnervation less likely to occur
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Generation of a resting membrane potential requires what? (2)
1) Unequal distribution of ions across the cell membrane
| 2) OPEN ion channels in resting membrane of cell
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Component of extracellular and intracellular ions
Extracellular
Cl-
Bacarb
Intracellular
Proteins A-
Phosphate
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What is the role of ion con difference and leak channels in generating resting membrane potential
Open K+ leak channels - cations flow out of cell.Inside cell is negative, Outside cell is positive
(Membrane polarization)
As membrane potential/voltage increases, the net outward diffusion of K+ decreases even if conc gradient don’t change (negative interior attract K+ back into cell)
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Hypokalemia lead to what?
| Hyperkalemia leads to what?
Hypokalemia - Hyperpolarization (more outward flow to reach equilibrium)
Hyperkalemia - Depolarization (less outward flow to reach equilibrium)
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How is Nernst equation different from the resting membrane potential in neurons?
Values obtained in neurons are less negative
(Additional ion permeability in neuron resting membrane)
Neuron permeable to both Na+ and K+. Resting membrane potential will be btwn -94 and 70 mV
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What different Goldman equation form Nernst equation?
Goldman is an extension of Nernst equation.
Goldman involve multiple ions, Nernst equation for only 1 ion
Vm = -67
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The membrane potential reached at equilibrium point when influx and effluent of an ion is balanced is called?
How is it calculated?
Equilibrium potential
Nernst equation for single ion
Goldman equation for multiple ions
135
Difference between membrane potentials of glial cells and neurons in comparison with the simplified model of cell.
Glial cells - similar to the simple model, however potassium leak channels can be manipulated which will change the glial cell resting membrane potential (hypokalemia- hyperpolarize)
Neurons- Na and K+ leak channels. Resting membrane potential is less negative (K going out more than Na coming in). Use Goldman equation- resting membrane btw -94 and 70
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How do you maintain the ion concentration gradient necessary for the resting membrane potential?
Through the activity of Na+K+ ATPase (use energy)
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How does the active and passive distribution of chloride ions affect the resting membrane potential?
Passive DIFFUSION of Cl- ; Cl- will alway be diffused out of the cell (interior of cell is negative at -67). Cl- DO NOT contribute to the resting membrane potential.
E.g SKELETAL MUSCLE - Cl-permeability is higher than resting K+ permeability
ACTIVE Transport
1) Na+K+2Cl- cotransport; 1Na, 1K, 2Cl transported INTO the cell, the energizer is Na+ (going down gradient). Used to maintain HIGHER INTERNAL Cl
2) K+Cl- cotransport - Transported OUT OF CELL. Energizer is K+. to maintain LOWER INTERNAL Cl. (-66mV)
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How do you maintain the ion concentration gradient necessary for the resting membrane potential?
Through the activity of Na+K+ ATPase (use energy)
139
How does the active and passive distribution of chloride ions affect the resting membrane potential?
Passive DIFFUSION of Cl- ; Cl- will alway be diffused out of the cell (interior of cell is negative at -67). Cl- DO NOT contribute to the resting membrane potential.
E.g SKELETAL MUSCLE - Cl-permeability is higher than resting K+ permeability
ACTIVE Transport
1) Na+K+2Cl- cotransport; 1Na, 1K, 2Cl transported INTO the cell, the energizer is Na+ (going down gradient). Used to maintain HIGHER INTERNAL Cl
2) K+Cl- cotransport - Transported OUT OF CELL. Energizer is K+. to maintain LOWER INTERNAL Cl. (-66mV)
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How does Hyponatremia and hypernatremia affect the resting membrane potential?
Hyponatremia (hypotonicity) - cerebral edema (decreased extracellular osmolarity)
Hypernatremia- increased osmolarity
Na+ don’t affect the resting membrane potential as much as K+
Na contributes to ACTION POTENTIAL and affects OSMOLARITY
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How does hypocalcemia and hypomagnesia affect resting membrane potential?
MEMBRANE SURFACE SCREENING - Ca and Mg help neutralize the negative charges on the extracellular surface of membrane
Decreased CA and Mg levels lead to LESS NEGATIVE membrane potential (unneutralized negative extracellular surface)
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What systems ARE/ARE NOT affected by the electrolyte disorders extracellular membrane
Affected- PNS, cardiac and skeletal muscle, other tissues
Not affected- CNS (isolated from the blood by blood-brain and blood-CSF barrier)
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What defines how easy a substance can move through a membrane?
What defines hw easy a ion can move through a membrane? How is it determined?
Membrane PERMEABILITY (Pm)
Membrane ION Permeability
Determined by the number of open ion channels
144
What defines how easy electric current flows through the cell membrane?
What is the inverse?
membrane conductance gm
Membrane resistance Rm = 1/g
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What defines the rate of charge or ion flow across a membrane?
2 requirements for ion to flow across membrane ?
Membrane current Im
Driving force
Conductance through membrane
Ohmn law
I= driving force ^v x g (conductance) or I= V/R
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Capability of cell membrane to store electrical charge is called
Capacitance Cm
| Quantified in farads- directly related to surface area of lipid bilayer of cell membrane
147
Measure of the rate at which a cell’s membrane potential changes in response to steady flow of current
MEMBRANE TIME CONSTANT
(Membrane resistance X membrane capacitance)
Resistance is inverse of conductance.
Conductance = # of open ion channels X single channel conductance
(To decrease membrane resistance -OPEN MORE ION CHANNELS)
Capacitance - directly proportion to surface area and inversely proportional to membrane thickness (e.d myelinated axon - very thick, Decreased capacitance)
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Distance over which change in membrane potential declines by approximately 63% from the original level?
How to calculate?
Length Constant
Square root of Rm/Ra
sq root of (membrane resistance/axial resistance)
Membrane resistance - depends on open ion channels (high resistance - no open channels )
Axial resistance- principle determinant is AXON DIAMETER (low diameter, high axial resistance)
149
Properties of Voltage gated Na+ channels
Has a VOLTAGE SENSOR -positively charged a.a and mobile (inward during resting membrane, outward and activated during depolarization -allow Na flow inside the cell)
Has a BALL and CHAIN -for inactivation (closes off the channel)
Axon of neuron membrane has lots of voltage gated Na channels for A.P
150
Measure of the rate at which a cell’s membrane potential changes in response to steady flow of current
MEMBRANE TIME CONSTANT
(Membrane resistance X membrane capacitance)
Resistance is inverse of conductance.
Conductance = # of open ion channels X single channel conductance
(To decrease membrane resistance -OPEN MORE ION CHANNELS)
Capacitance - directly proportion to surface area and inversely proportional to membrane thickness (e.d myelinated axon - very thick, Decreased capacitance)
151
Distance over which change in membrane potential declines by approximately 63% from the original level?
How to calculate?
Length Constant
Square root of Rm/Ra
sq root of (membrane resistance/axial resistance)
Membrane resistance - depends on open ion channels (high resistance - no open channels )
Axial resistance- principle determinant is AXON DIAMETER (low diameter, high axial resistance)
152
Properties of Voltage gated Na+ channels
Has a VOLTAGE SENSOR -positively charged a.a and mobile (inward during resting membrane, outward and activated during depolarization -allow Na flow inside the cell)
Has a BALL and CHAIN -for inactivation (closes off the channel)
Axon of neuron membrane has lots of voltage gated Na channels for A.P
RISING PHASE
153
Properties of Voltage gated K+ channels
delayed rectifier channels
VOLTAGE SENSOR
SLower activation rate compared to Na
NO BALL AND CHAIN- No fast inactivation
Open K+ channel- K+ flow out of cell - hyperpolarize (open NEAR PEAK of A.P) - FALLING PHASE of A.P
channels close slowly- lead to undershoot (-80) - K+ more permeable than Na (50:1)
154
Absolute refractory period (cause and hw it ends)?
Relative refectory period (cause and how it ends)?
Absolute - time period when another A.P CAN NOT be generated
(Caused by inactivation of VGNa+ channels at PEAK of A.P and it ends when Na+ recover from inactivation )
Relative- time period when another AP can be generated but the current to generate it is too HIGH
(Caused by SLOW CLOSING OF delayed rectifier K+ channels and some inactivated Na+ channels )
155
Toxins and drugs that affect Voltage Na+ channels (6)
1) Tetradotoxin TTX- Virulent poison from PUFFER FISH, blocks Na channels, fatal in small doses
2) Saxitoxin (STX) Shell fish/ marine dinoflagellates responsible for RED TIDE- Blocks VGNa+ channels, PARALYTIC shellfish poisoning
3) Local anesthesia - Lidocaine/derivation of COCAINE - block VGNa+ channels.
4) Anti Arrhythmia - Lidocaine, Mexilletine - PARTIAL BLOCKAGE of cardiac VGNa+ help control arrthymias
5) Anti-epileptic - control seizures by promoting inactivation/refractory state -can’t fire AP at high rate
6) Other toxins - Poison-dart frogs (batrachotoxin), Scorpion toxin, plant toxin (buttercup and lily families)
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What is USE- DEPENDENCE? Which drugs have this property? Which drug/toxin don’t?
Local ANESTHETICS and ANTIARRHYMICS drugs block VGNa+ channels by binding to the channels in OPEN state
Tetrodotoxin (Puffer fish) and Saxitoxin (shell fish) bind in the OUTER MOUTH of the channel pore - don’t require channel to be in open state to block VGNa+ channels
157
What compounds affect VGK+ channels?
TEA- tetraethylammonium
4-aminopyridine
Some ions (Barium, cesium)
Block delayed rectifier K+ channels - increase duration of A.P and shorten the refractory period - ENHANCE A.P INITIATION
POISONING OF these compounds lead to CONVULSIONS
** Aminopyridines improve symptoms in some patients with MS
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What refers to the relationship btw the magnitude of sustained depolarization (depends on stimulus intensity) and the RATE of A.P generation.
FREQUENCY CODING
- a way for the nervous system to signal the intensity of a stimulus (by the firing rate)
159
How is A.P generated in unmyelinated axons (Invertebrates)?
Conduction velocity/ speed of A.P propagation?
What are drawbacks?
Continuous REGENERATION
VGNa+ channels accumulate in initial segment of axon, CAPACITIVE CURRENT progress ahead of A.P down the axon bringing it to to threshold) Firing in initial segment regenerate A.P in other segments (ORTHODROMIC direction)
PRINCIPLE determinant of CONDUCTION VELOCITY in UNMYELINATED axon is LENGTH CONSTANT (Increase axial diameter to reduce resistance and increase the length constant)
Drawbacks: Increase axon diameter will INCREASE surface area and INCREASE membrane capacitance and membrane TIME CONSTANT which DECREASE rate of membrane potential change and DECREASE A.P regeneration . CAN NOT be used for human CNS - MASSIVE HEAD
160
Action potential propagation in MYELINATED axons (Vertebrates)? INTERNODAL SEGMENTS of axons (btw nodes)
1) Alter the distribution of ion channels
-VGNa+ channels concentrated in the NODES OF RANVIER
—VGK+ channels in NODES and JUXTAPArANODE
2) Alter the length and time constant
- INCREASE length constant by INCREASE in membraneRESISTANCE
- DECREASED membrane CAPACITANCE - NO INCREASE in time constant
Both alterations lead to SALTATORY CONDUCTION -A.P jump rapidly from one node of Ranvier to the next
161
Conduction velocity of myelinated axons vs unmyelinated axons
Myelinated - 120 m/sec
Unmyelinated - 0.5 -2m/sec
162
2 Demyelinating diseases ad what is affected?
1) MULTIPLE SCLEROSIS (MS)- affect CNS myelin - Oligodendrocytes
2) GBS- Guillian Barre Syndrome - affect PNS myelin - Schwann cells
* *DECREASE conduction velocity
- SENSORY AND MOTOR disturbances
163
Which drug can be given to a MS patient? How will it help?
4-Aminopyridine
-Improve axon function by BLOCKING VGK+ channels in the juxtaparanodal region (region is exposed by demyelination)
164
Name the Ion channel(s)?
- alpha subunit is one large protein with 4 repeated domains
- Has ball-and chain for rapid inactivation
- Has voltage sensor that move outward during activation
Na+ and Ca+ channels
Ball and chain for Na+ btw domains 3 and 4
Ball and chain for Ca is btw domain 1 and 3
Voltage sensor is in S4 segment
165
Name the ion channel
—Has 4 smaller separate alpha subunit that assemble to form main functional protein
-Has Voltage sensor in S4 transmembrane segment
-No ball and chain- no fast inactivation
K+ channel
166
Name the ion channel(s)
-Has P-loop in outer mouth/vestibule of pore of ion channel - forms slelecivity filter -control ion selectivity and permeability of channel
Na+, Ca+ and K+
