1
Q
Learning issues
A
Histology of the neuron and supporting cells of the nervous system (Pawlina parts of ch12)
Biochemistry of tissue metabolism (muscle) [Ch 45 Marks]
Receptor types of pharmacology (Katzung parts of Ch 2)
2
Q
neurons*
A
- The structural and functional unit of the nervous system. They transmit and relay signals, and don’t divide into adulthood.
- Axons do not have RER.
3
Q
astrocytes*
A
These are the most common glial cell type in the CNS. They provide physical support, repair, extracellular K buffer, removal of excess transmitters, component of the blood brain barrier, and glycogen fuel reserve buffer. Will produce reactive gliosis in response to neural injury.
4
Q
Wallerian degeneration*
A
Degeneration of the axon distal to the site of injury and axonal retraction proximally. Allows for partial regeneration of the axon, if in the PNS. Macrophages will remove the debris and myelin.
5
Q
microglia*
A
- phagocytic cells that proliferate and become phagocytotic (reactive microglial cells) in regions of disease or injury
- defend against invading microorganisms and neoplastic cells. Remove bacteria, injured cells, debris of cells from apoptosis; mediate neuroimmune reactions
- Not readily discernible by Nissl stain.
6
Q
ependymal cells*
A
- form an epithelial-like lining of ventricles of the brain and spinal cord, and other fluid-filled cavities
- form single layer of cuboidal-to-columnar cells, no external lamina, apical surfaces have cilia (circulates CSF) and microvilli (absorbs CSF)
7
Q
what is located within the nodes of ranvier?*
A
have a high concentration of Na+ channels
8
Q
Schwann cells*
A
each Schwann cell myelinates only 1 PNS axon. Also promotes axonal regeneration, derived from the neural crest.
9
Q
Oligodendrocytes*
A
Myelinates neurons in the CNS. Each one is able to myelinate many axons. This is the predominant type of glial cell in white matter. “Fried egg” appearance histologically
10
Q
what are the different parts of the peripheral nerve?*
A
nerve trunk, which refers to the entire structure, then the layers of the epineurium, perineurium, endoneurium, then the nerve fiber in the inside
11
Q
endoneurium*
A
invests single nerve fiber layers
12
Q
perineurium*
A
surrounds a fascicle of nerve fibers, blood nerve Permeability barrier
13
Q
epineurium*
A
dense connective tissue that surrounds the entire nerve (fascicle and blood vessels)
14
Q
what are the layers of the meninges?*
A
dura, arachnoid, and pia
15
Q
dura mater*
A
a thick outer layer of the meninges closest to the skull, derived from the mesoderm
16
Q
arachnoid mater*
A
middle layer of the meninges, contains web-like connections. Derived from the neural crest.
17
Q
pia mater*
A
thin, fibrous inner layer of the meninges that firmly adheres to the brain and spinal cord. Derived from the neural crest.
18
Q
subarachnoid space*
A
located between the arachnoid and pia mater, where the CSF is located
19
Q
epidural space*
A
potential space between the dura mater and skull, contains fat and blood vessels
20
Q
neuroglia/glia cells
A
nonconducting cells that are located close to the neuron
21
Q
central neuroglia and types
A
central neuroglia are the types of glial cells in the CNS
oligodendrocytes, astrocytes, microglia, and ependymal cells
22
Q
peripheral neuroglia and types
A
supporting cells in the PNS
Schwann cells, satellite cells, terminal neuroglia aka teloglia (associated with motor end plate), enteric neuroglia (associated with ganglia in alimentary canal), Muller’s cells (in retina)
23
Q
ganglia
A
collections of nerve bodies outside the CNS
24
Q
enteric neuroglial cells
A
supporting cells of the ganglia in the wall of the alimentary canal
25
what are the 3 general categories of neurons?
sensory, motor, and interneuron
26
sensory neurons, where they can be found
neurons that convey impulses from receptors to the CNS. Their processes are included in somatic afferent and visceral afferent nerve fibers.
27
motor neurons
- convey impulses from the CNS or ganglia to effector cells
| - their processes can be included in somatic efferent and visceral efferent nerve fibers
28
interneurons
aka intercalated neurons. They form a communicating and integrative network between sensory and motor neurons. Vast majority of neurons.
29
cells of the autonomic nervous system
- smooth muscle
- cardiac conducting cells called Purkinje fibers
- glandular epithelium
30
where are the cell bodies of sensory neurons located?
dorsal root ganglia and cranial nerve ganglia
31
what are the parts of the cell body of the neuron?
- large, euchromatic nucleus with nucleolus
- surrounding perinuclear cytoplasm
- Nissl bodies are small bodies of ribosomal in stacks of rER that stain with basic dye
32
axon hillock
area of the cell body that corresponds to the site of the axon. Lacks cytoplasmic organelles and distinguishes axons from dendrites.
33
dendrites
receptor processes that receive stimuli from other neurons or from the external environment
34
dendritic spines
- most excitatory neurons have these protrusions from their membrane
- involved in synaptic plasticity, learning, and memory formation
- have a postsynaptic density that has transmitters and voltage gated Na and K channels
35
what transmitter is typically in the synapse between dendritic spines and axons?
glutamate (GLU), which mediates fast excitatory synaptic transmission in the CNS
36
axon
- conveys information away from the cell body to another neuron or effector cell
- each neuron has ONE axon
37
axon initial segment (AIS)
- surface region of the axon between the apex of the axon hillock (origin of the axon) and the beginning of the myelin sheath
- acts as a diffusion barrier to exclude passage of molecules or vesicles that don't belong to axonal membrane
- action potential is generated here
38
organization of microtubules in axons vs dendrites
- microtubules are composed of tubulin heterodimers with plus end where they elongated, and minus end where they are anchored
- microtubules in axons are oriented with their plus ends directed distally
- microtubules in dendrites have a mixed polar orientation
39
axonal transport, types
- supplies the distal part of the axon and its terminal with newly synthesized proteins, lipids, and neurotransmitters for synaptic transmission
- anterograde and retrograde transport
40
anterograde transport, and protein involved
- carries material from the nerve cell body to axon periphery
- kinesins, microtubule-associated motor proteins, move transport veiscles for axons along microtubules towards their plus end, use ATP energy
41
retrograde transport, and protein involved
- carries material from axon terminal to nerve cell body
- mediated by microtubule-associated motor proteins called dyneins that travelalong microtubules toward minus ends
- toxins and viruses use this pathway to enter the CNS at nerve endings
42
which proteins are mostly involved in dendritic transport? Which type of transport do they mediate?
- dynein molecular motors
| - use anterograde transport to move things into dendrites, and retrograde transport moving things from dendrites
43
boutons en passant
the axon of the presynaptic neuron travels along the surface of the postsynaptic neuron, and makes these synaptic contacts
44
what mediates the binding and fusion of synaptic vesicles in the presynaptic plasma membrane?
a family of transmembrane proteins called SNAREs, e.g. synaptobrevin, syntaxin, SNAP-25, which are target-membrane bound t-SNARE proteins in the presynaptic membrane
45
which protein will displace the SNARE complex?
synaptotagmin 1
46
porocytosis
an alternative process that releases transmitters.
- synaptic vesicles gets anchored to presynaptic membrane next to Ca-selective channels by SNARE and synaptotagmin proteins
- with Ca, the vesicle and presynaptic membranes are reorganized and create a fusion pore that connects lumen of vesicle with synaptic cleft, where transmitters are released through
47
which receptors do ACh act on, and their subtypes?*
- ionotropic nicotinic ACh receptors are ligand-gated Na K channels. Two subtypes are NN and NM
- metabotropic muscarinic ACh receptors, that are G protein coupled receptors to open K channels. 5 subtypes M1-M5
48
cholinergic neurons
neurons that use ACh as their neurotransmitter
49
catecholamines
- neurotransmitters synthesized from enzymatic reactions involving tyrosine
- examples are norepinephrine, epinephrine, dopamine
- secreted by cells in the CNS that are involved in regulation of movement, mood, attention
50
adrenergic neurons
-neurons that use epinephrine as the neurotransmitter. Convert norepinephrine to epinephrine (adrenaline), which is involved ebtween postsynaptic sympathetic axons and effectors in the ANS
51
small peptides
- many are synthesized and released by enteroendocrine cells of intestinal tract, endocrine organs, or hypothalamus
- can act on neighboring cells (paracrine secretion) or be carried as hormones in bloodstream to act on distant cells (endocrine secretion)
- examples are substance P, hypothalamic-releasing hormones, endogenous opioid peptides (beta-endorphin, enkephalins, dynorphins), vasoactive intestinal peptide (VIP), cholecystokinin (CCK), neurotensin
52
high-affinity reuptake
- most common process of neurotransmitter removal after its release into the synaptic cleft
- transmitters get bound to specific neurotransmitter transport proteins in presynaptic membrane
- neurotransmitters that get transported into presynaptic bouton are either destroyed by enzymes or reloaded into empty synaptic vesicles
53
how do Schwann cells differentiate form from the neural crest cells?
they differentiate by expressing transcription factor sox-10
54
satellite cells
- small cuboidal cells that surround the neuronal cell bodies of the ganglia
- functional role is analogous to Schwann cell; they establish and maintain controlled microenvironment around neuronal body, provide electrical insulation and pathway for metabolic exchange
55
protoplasmic astrocytes
- prevalent in outermost covering of gray matter in brain. They have numerous short, branching cytoplasmic processes.
- extend to basal lamina of pia to form an impermeabale barrier surrounding the CNS called the glia limitans
56
fibrous astrocytes
more common in inner core of the brain called the white matter. Have fewer processes and are relatively straight.
57
differences between myelin in CNS and PNS
- CNS myelin has fewer Schmidt-Lanterman clefts (cytoplasm in myelin) because astrocytes provide metabolic support for CNS neurons
- oligodendrocytes have no external lamina, and little cytoplasm in external layer, adjacent axons may touch
- CNS has larger nodes of ranvier, so larger areas of exposed axolemma and more efficient saltatory conduction
- unmyelinated CNS axons are really bare, not embedded in glial cell processes
58
choroid plexus
within the system of brain ventricles, the epithelium-like lining of ependymal cells is modified to produce CSF from materials from capillary loops.
59
what are the subtypes of nicotinic ACh receptors?*
- Nn found in autonomic ganglia, adrenal medulla
| - Nm found in neuromuscular junction of skeletal muscle
60
what are the subtypes of muscarinic ACh receptors?*
M1 in heart, M2 in smooth muscle, M3 in brain, M4 in exocrine glands, M5 on sweat glands (cholinergic sympathetic)
61
agonists
they activate the receptor to signal as a direct result of binding to it
62
antagonists
they bind to receptorsbut do not activate generation ofa signal; they interfere with the ability of an agonist to activate the receptor
63
what is the concentration-effect curve like with the receptor binding of agonists and why?
- responses to low doses of a drug usually increase in direct proportion to the drug
- dose increases and response increment diminishes
- eventually response saturates
- drug concentration vs effect is a hyperbolic curve
64
how does Kd relate to binding affinity?
low Kd means binding affinity is high, and vice versa
65
what will be the effect of adding a competitive antagonist to the agonist dose vs percent of maximum effect curve?*
- adding a competitive antagonist along with the agonist will inhibit the agonist response
- shifts the curve to the right and decrease potency
- can be overcome by increasing the concentration of the agonist substrate, so Emax stays the same
66
what are receptor reserves/ spare receptors?
receptors are spare for a given pharmacologic response if it is possible to elicit a maximal biologic response at a concentration of agonist that does not result in occupancy of all available receptors
67
what will be the effect of adding a noncompetitive/irreversible antagonist to the agonist dose vs percent of maximum effect curve?*
- adding a noncompetitive/irreversible antagonist reduces the maximal effect the agonist can achieve
- the curve is shifted down and efficacy is reduced
68
noncompetitive antagonist
- these drugs bind to receptors and agonists won't be able to overcome their inhibitory effect, regardless of agonist concentration
- considered irreversible and may form a covalent bond with the receptor
69
what effect do partial agonists have?
- partial agonists do not cause maximal pharmacologic response even when they saturate receptors
- partial agonists competitively inhibit the responses produced by full agonists, compete with full agonists for receptor sites, has mixed agonist/antagonist properties
70
how does the agonist dose vs. percent of maximum effect curve change with a partial agonist vs full agonist?*
- the partial agonist acts at the same site as the full agonist, but with lower maximal effect, decreased efficacy. Potency is an independent variable.
- curve for partial agonist is a shallower curve and reaches a lower maximum
71
how are intracellular receptors for lipid soluble agents activated, what are some classes of these agents?
- some biologic ligands are lipid soluble enough to cross the plasma membrane and act on intracellular receptors
- often include steroids and thyroid hormone
72
what do the receptors of lipid soluble agents bind to, and what effect does this have?
- they stimulate the transcription of genes by binding to specific DNA sequences (ie response elements) near the gene whose expression is to be regulated
- takes half to several hours to take effect and synthesize new proteins, and their effects can last for hours or days after agonist gone
73
how is the receptor tyrosine kinase signaling activated, what does it do?
- ligand (usually hormone or growth factor) binds to receptor's extracellular domain, conformational change
- two receptors bind to one another and dimerize, activates tyrosine kinase enzyme in cytoplasmic domain
- phosphorylates receptor and downstream signaling proteins
74
receptor down-regulation
- ligands bind to receptors and cause endocytosis of receptors from cell surface, and then degradation of the receptors and ligands
- may be broken down faster than remade, so cell-surface receptors are down-regulated, and cell is less responsive to the ligand. Especially concerns receptor tyrosine kinases
75
how are cytokine receptors activated and what effect do they have?
- respond to group of peptide ligands, like growth hormones and growth factors
- has a separate tyrosine kinase protein from Janus-kinase (JAK) family that binds noncovalently to the receptor
- ligand binds, cytokine receptors dimerize, activate JAKs, phosphorylates tyrosine residues, bind to STAT proteins, phosphorylated by JAKs, dimerize
- STAT/STAT dimer dissociates from receptor and travels to nucleus to regulate transcription of specific genes
76
G protein-coupled receptors definition and structure
- receptors that signal G proteins
| - seven-transmembrane (7TM) where receptor polypeptide chain snakes across plasma membrane seven times
77
what is cAMP?
cAMP is an intracellular messenger that mediates hormonal responses
78
how does cAMP exert its effects?
- cAMP stimulates cAMP-dependent protein kinases
- kinases have a cAMP-binding regulatory (R) dimer and two catalytic (C) chains
- cAMP binds to R, active C chains are release and diffuse through cytoplasm to nucleus
- they transfer phosphate from ATP to substrate proteins
79
what is the effect of cGMP?
- stimulates cGMP-dependent protein kinase
| - increased cGMP concentration causes relaxation of vascular smooth muscle
80
amplification in phosphorylation
the attachment of a phosphoryl group to serine, threonine, or tyrosine residue will amplify the initial regulatory signal by recording a molecular memory that the pathway has been activated
81
efficacy of a drug and interpretation on log drug dose vs. percent maximum effect curve*
- maximal effect a drug can produce
- On a graph of log drug dose vs percent maximum effect, it is the y-value where the Vmax is. Drugs with a higher y value have a higher Vmax and have higher efficacy.
- unrelated to potency
82
potency of a drug and interpretation on log drug dose vs. percent maximum effect curve*
- amount of the drug needed for a given effect
- On a graph of log drug dose vs percent maximum effect, it is given by EC50 (concentration of the drug to give half the maximal effect) on the x-axis. Shifting to the left decreases EC50, increases potency, and decreases the drug needed
- unrelated to efficacy
83
which enzyme is a key regulator of muscle glycolysis, how is it different from the same enzyme in the liver?
- phosphofructokinase-2, which phosphorylates cAMP
| - different from liver PFK-2, not inhibited by phosphorylation
84
what role to muscles play in fatty acid metabolism, which enzymes are involved in this?
- muscle cells do not synthesize fatty acids, but they regulate the rate of fatty acid oxidation
- use acetyl coenzyme A carboxylase (ACC-2), and malonyl-CoA decarboxylase
85
what do muscles use to store high-energy bonds, and which enzyme makes this?
- muscles use creatine phosphate to store high-energy bonds
| - creatine phosphokinase (CPK) catalyzes reversible transfer of high-energy phosphate to ATP to creatine
86
what controls fatty acyl-CoA uptake in the skeletal muscle? How is this regulated?
- malonyl-CoA controls fatty acyl coenzyme A (fatty acyl-CoA) uptake into mitochondria
- in muscle, malonyl-CoA is produced by ACC-2
- ACC-2 is inhibited by phosphorylation of AMPK, so if energy levels are low, malonyl-CoA levels are low, triggers mitochondria to allow fatty acid oxidation
87
how is malonyl-CoA decarboxylase activated in the muscle, what effect does it have?
- phosphorylation of AMPK activates the enzyme malonyl-CoA decarboxylase
- malonyl-CoA decarboxylase converts malonyl-CoA to acetyl-CoA
- relieves inhibition of CPTI and stimulates fatty acid oxidation
88
how does the skeletal muscle use creatine phosphate?
create phosphate donates a phosphate group to ADP to regenerate ATP for muscle contraction
89
what places get priority for metabolic fuel use during fasting and starvation?*
priorities are to supply sufficient glucose to the brain and the RBCs to preserve protein
90
what metabolic processes dominate during a fed state, and what regulates these?*
- glycolysis and aerobic respiration
| - insulin will stimulate the storage of lipids, proteins, and glycogen
91
what metabolic processes dominate during a fasting (between meals) state, and what regulates these?*
- hepatic glycogenolysis (major); hepatic gluconeogenesis, adipose release of FFA (minor)
- glucagon and epinephrine stimulate the use of fuel reserves
92
what metabolic processes dominate during starvation (days 1-3)?*
- blood glucose levels will be maintained by hepatic glycogenolysis, adipose release of FFA, muscle and liver (shift from using glucose to FFA), hepatic gluconeogenesis from peripheral tissue alanine and lactate, and from adipose tissue glycerol and propionyl-CoA (from odd-chained FFA)
- glycogen reserves are depleted after 1 day
- RBCs have no mitochondria and can't use ketones
93
what metabolic processes dominate during starvation (days 3+)?*
- adipose stores, and ketone bodies become the main energy source for the brain
- after these are depleted, vital protein degradation accelerates, leads to organ failure and death
94
what kind of metabolism happens at onset of exercise, what is the fuel source?
glycogen is converted to lactate to provide ATP requirement; anaerobic glycolysis happens
95
what kind of metabolism in type 2b fibers (what are these), where does it get its fuel source and what is this pathway?
- type 2b are fast twitch glycolytic fibers
- uses glycogen and creatine phosphate to generate ATP
- glycogen to glucose 1-phosphate, to glucose 6-phosphate, to lactate
96
what will trigger anaerobic glycolysis from glycogen in muscle?
AMP will allosterically activate PFK-1 and glycogen phosphorylase b
97
what enzyme regulates AMP phosphorylation in muscle?
myokinase/ adenylate kinase keeps the equilibrium of 2ADP reverse arrows AMP +ATP
98
what causes muscle fatigue/metabolic fatigue in muscles?
- aerobic and anaerobic metabolism will lower pH
- lactate production
- muscle glycogen gets depleted
99
how is muscle glycogen metabolism regulated?
- there are no glucagon receptors in muscle, so its glycogen doesn't get degraded by glucagon
- release of insulin activates glycogen synthase
- muscle glycogen phosphorylase b can bind to AMP, and this activates myosin-ATPase and accumulates AMP; enhances glycogen degradation
- activators of muscle glycogen phosphorylase b include calcium, epinephrine to adenylate cyclase to cAMP dependent protein kinase
100
what metabolic pathways are used during high intensity exercise?
- exercise increases ADP and decreases ATP
- activates electron transport chain, TCA, and fatty oxidation
- strenuous, high activity exercise may need more ATP
- increased AMP levels activate PFK-1 and glycogenolysis, create more ATP through anaerobic glycolysis
101
fate of lactate released during exercise
- lactate can be released during exercise
- may be used by resting skeletal muscles or heart
- low NADH/NAD+ ratio allows lactate dehydrogenase reaction to create pyruvate from lactate
- pyruvate becomes acetyl-CoA and enters TCA and produces energy with oxidative phosphorylation
- lactate may go into Cori cycle in liver
102
what does training do to muscle?
- increases muscle glycogen stores and increase the number and size of the mitochondria
- fibers can generate more ATP from oxidative metabolism and can use fatty acids as fuel
103
how is lactate release affected by duration of mild/moderate exercise?
during mild and moderate intensity exercise, release of lactate acid diminishes as aerobic metabolism of glucose and fatty acids becomes predominant, because it is more efficient at producing energy
104
how is blood glucose levels maintained during exercise?
- blood glucose must be constantly replenished during exercise
- liver produces glucose by breaking down its own glycogen stores by gluconeogenesis then glycogenolysis
- AMP levels increase, activate AMPK, GLUT4 translocates to muscle membrane and allows glucose uptake to muscle
105
what fuel source do the muscles rely on with longer durations of exercise, how is it used as fuel source?
- longer duration of exercise means more reliance on free fatty acids to generate ATP
- free fatty acids generate ATP with mitochondria and oxidative phosphorylation
106
what are branched chain amino acids important for in muscle metabolism?
BCAAs can be oxidized to supply some ATP to resting muscles. It also synthesizes glutamine.
107
what is the purine nucleotide cycle important for in muscle metabolism?
- exercise will increase purine nucleotide cycle
- produces ammonia, which can buffer proton production from lactate production; fumarate produced can be recycled to form glutamine
108
what is acetate used for in muscle metabolism?
- provides a fuel source for skeletal muscle
| - treated like very short chain fatty acid, to acetyl CoA
109
what is the main function of the blood brain barrier?*
prevents circulating blood substances (e.g. bacteria and drugs) from reaching the CSF/CNS
110
what structures form the BBB?*
- tight junctions between nonfenestrated capillary endothelial cells
- basement membrane
- astrocyte foot processes
111
what is able to cross the BBB?*
- glucose and amino acids can cross slowly by carrier-mediated transport mechanisms
- nonpolar/lipid-soluble substances cross rapidly via diffusion
DPC
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