Chapter 11: Neuromuscular Physiology Flashcards
(80 cards)
1
Q
How does acetylcholine interact with nicotinic acetylcholine receptors (nAChRs)?
A
- Acetylcholine binds to the α subunits of the nAChRs.
- Binding occurs when two acetylcholine molecules cooperatively attach to sites on the extracellular surface of the receptor.
2
Q
What triggers the opening of ligand-gated cation channels at the neuromuscular junction (NMJ)?
A
- The channels open almost instantaneously when two acetylcholine molecules bind to the nAChRs, causing a conformational shift in the subunits.
3
Q
What happens at the cellular level when acetylcholine binds to nAChRs?
A
- Sodium ions flow down their electrochemical gradient into the muscle cell, depolarizing the muscle cell membrane at the NMJ.
- Simultaneously, potassium exits the cytosol of the muscle fiber.
4
Q
What is the effect of depolarization on voltage-gated calcium ion channels in the motor nerve?
A
- Opens voltage-gated calcium ion channels, which triggers the mobilization of synaptic vesicles (SVs)
- Activates the fusion machinery in the nerve terminal, leading to the release of acetylcholine.
5
Q
What is the function of potassium channels in the nerve terminal during neurotransmitter release?
A
- Limit the extent of calcium ion entry and neurotransmitter release.
- They help initiate repolarization of the nerve terminal, thus regulating the process.
6
Q
How does depolarization at the muscle membrane activate sodium channels?
A
- Depolarization activates voltage-gated sodium channels present in the muscle membrane.
- These channels mediate the initiation and propagation of action potentials across the muscle membrane.
7
Q
What is the role of sodium channels in the muscle membrane regarding action potentials?
A
- Are responsible for the upstroke of the action potential.
- Facilitating its propagation across the muscle surface and into the transverse tubules (T tubules).
8
Q
What are the two types of calcium channels involved in muscle contraction?
A
- Dihydropyridine receptor (DHPR) in the T tubules and the
- Ryanodine receptor 1 (RyR1) in the sarcoplasmic reticulum (SR).
9
Q
What is the role of dihydropyridine receptors (DHPRs) in muscle contraction?
A
- Act as “voltage sensors” and are activated by membrane depolarization.
- Their activation, in turn, triggers the activation of RyR1 receptors.
10
Q
What happens during the DHPR-RyR1 interaction in muscle cells?
A
- Releases large amounts of calcium ion from the sarcoplasmic reticulum (SR).
- Leading to a transient increase in myoplasmic free calcium ion concentration.
11
Q
How does calcium ion contribute to muscle contraction?
A
- The increased myoplasmic calcium ion binds to troponin C, initiating the movement of tropomyosin on the thin filament (actin).
- This allows cross-bridges to form between myosin and actin, resulting in force development, a process known as excitation-contraction coupling.
12
Q
What role does the calcium ion pump play in muscle relaxation?
A
- The calcium ion pump in the SR actively reaccumulates calcium ions, lowering their concentration in the sarcoplasm.
- This process, powered by ATP, stops cross-bridging between myosin and actin, leading to muscle relaxation.
13
Q
What is the consequence of the failure of the calcium ion pump in skeletal muscles?
A
- Results in sustained skeletal muscle contraction
- Increased heat production, leading to malignant hyperthermia.
- The RyR1 gene, associated with malignant hyperthermia susceptibility, is located on chromosome 19.
14
Q
How is repolarization of the muscle membrane initiated?
A
- Begins with the closing of sodium channels and the opening of potassium (K+) channels, which conduct an outward K+ current.
15
Q
How does the muscle membrane potential return to its resting level?
A
- The muscle membrane potential returns to its resting level (approximately −70 to −90 mV)
- By allowing chloride (Cl−) ions to enter the cell through voltage-sensitive chloride channels.
16
Q
How much can skeletal muscle blood flow increase during strenuous exercise?
A
- More than 20 times during strenuous exercise,
- The greatest increase of any tissue in the body.
17
Q
What percentage of capillaries are open in skeletal muscles at rest, and how does this change during exercise?
A
- At rest, only 20% to 25% of the capillaries in skeletal muscles are open.
- During strenuous exercise, almost all capillaries become patent.
18
Q
What are the benefits of opening previously collapsed capillaries in muscles during exercise?
A
- Reduces the diffusion distance for oxygen and nutrients to skeletal muscle fibers.
- Increases the surface area for nutrient diffusion.
19
Q
What causes vasodilation in skeletal muscles during exercise?
A
- Exercise reduces local oxygen concentration, leading to vasodilation.
- Possibly due to the vessel walls’ inability to maintain contraction without oxygen or the release of vasodilators like K+ and adenosine.
20
Q
How does exercise affect cardiac output?
A
- The increase in cardiac output during exercise is mainly due to local vasodilation in active skeletal muscles
- Increased venous return to the heart.
21
Q
What is the effect of exercise on the sympathetic nervous system and systemic blood pressure?
A
- Triggers a centrally mediated sympathetic response, causing vasoconstriction in nonmuscular tissues
- Increases in systemic blood pressure, but excessive pressure increases are moderated by vasodilation in skeletal muscles.
22
Q
Which circulations are exceptions to the nonmuscular tissue vasoconstriction induced by exercise?
A
- Thecoronary and cerebral circulationsare exceptions
- They do not undergo vasoconstriction during exercise, vital for the response to exercise along with skeletal muscles.
23
Q
What role does the calcium ion pump play in muscle relaxation?
A
- The calcium ion pump in the SR actively reaccumulates calcium ions, lowering their concentration in the sarcoplasm.
- This process, powered by ATP, stops cross-bridging between myosin and actin, leading to muscle relaxation.
24
Q
How is smooth muscle anatomically distinguished from skeletal and cardiac muscle?
A
- Smooth muscle lacks visible cross-striations as actin and myosin are not arranged in regular arrays.
25
What are the two categories of smooth muscle?
- Multiunit
- Visceral smooth muscle.
26
What characterizes multiunit smooth muscle?
- Multiunit smooth muscle contraction is controlled almost exclusively by nerve signals, with spontaneous contractions being rare.
- Examples include the ciliary muscles of the eye and smooth muscles of many large blood vessels.
27
How do calcium ions enter smooth muscle cells?
* In smooth muscle, the sarcolemma contains caveoli, which are saclike inpocketings where calcium ions may enter through voltage-gated calcium ion channels.
28
What types of calcium ion channels are found in the sarcoplasmic reticulum (SR) of smooth muscles?
* RyR1 channels (similar to skeletal muscles)
* Inositol 1,4,5-triphosphate (IP3)-gated calcium ion channels.
29
What is unique about visceral smooth muscle?
* Visceral smooth muscle often forms a functional syncytium
- undergoes spontaneous contractions as a single unit
- particularly prominent in tubular structures for peristaltic motion.
30
What is notable about the action potentials in visceral smooth muscle?
* Visceral smooth muscle can have plateaus in action potentials lasting up to 30 seconds, especially in the ureters and uterus, with a resting transmembrane potential of approximately −60 mV.
31
How does smooth muscle respond to hormones and local tissue factors?
* Uniquely sensitive to hormones and local factors, which
- Can cause contraction by activating calcium ion transport or
- Relax the muscle by increasing cyclic adenosine or guanosine monophosphate.
32
What proteins are involved in smooth muscle contraction, and how do they differ from skeletal muscle?
- Smooth muscles contain actin and myosin.
- Skeletal muscles, they lack troponin and are innervated by autonomic neurons.
33
How does the calcium-calmodulin complex contribute to smooth muscle contraction?
* The calcium-calmodulin complex activates the enzyme necessary for phosphorylation of myosin
* Leading to actin sliding on myosin and producing contraction.
34
What is the primary source of calcium in smooth muscle contraction?
Comes from extracellular fluid during action potentials, as the SR in smooth muscle is poorly developed.
35
How does the duration of smooth muscle contraction compare to that of skeletal muscle?
* The duration of smooth muscle contraction is often seconds, much longer than skeletal muscle contractions
* Due to the slow calcium ion transport system.
36
What happens to smooth muscles when they are denervated?
* Smooth muscles do not atrophy when denervated but become hyperresponsive to normal neurotransmitters
* due to the synthesis or activation of more receptors.
37
Describe the arrangement of nerve fibers in smooth muscle.
* In smooth muscle, nerve fibers branch diffusely over the muscle fibers without making actual contact.
- secreting neurotransmitters into the interstitial fluid.
38
How do acetylcholine and norepinephrine function in smooth muscle?
* Acetylcholine can be excitatory or inhibitory in smooth muscles, depending on the site.
* Norepinephrine often exerts the opposite effect.
39
What characterizes the electrical and contractile activity of uterine smooth muscle?
* Uterine smooth muscle exhibits a high degree of spontaneous electrical and contractile activity
- with contractions spreading from cell to cell at a rate of 1 to 3 cm/s.
40
What are the peak intrauterine pressures during the second stage of labor?
- Peak intrauterine pressures can reach 60 to 80 mm Hg.
- Resting uterine pressure is approximately 10 mm Hg.
41
What ion movement is key in uterine depolarization and contraction?
- Sodium ion movement is the primary determinant in depolarization of the uterine smooth muscle.
- Calcium ions are necessary for excitation-contraction coupling.
42
How does calcium ion availability influence uterine smooth muscle?
* Influences the response of uterine smooth muscle to both physiological and pharmacological stimuli.
43
What types of receptors are present in uterine smooth muscle (myometrium)?
- α excitatory receptors
- β inhibitory receptors.
44
What are the components of the Neuromuscular Junction (NMJ)?
- Motor neuron
- Muscle fiber
- Schwann cells.
45
How does innervation at the NMJ change postnatally?
* Initially, muscle fibers are innervated by multiple motor nerves.
* This transitions to single innervation within a few days postnatally.
46
Describe the structure of motor nerve endings at the NMJ.
* The motor nerve ending branches and invaginates into the skeletal muscle fiber outside the sarcolemma.
* Schwann cells cap the naked motor nerve terminals not in contact with the muscle fiber.
47
What are the structural components of the NMJ?
1. Presynaptic nerve terminal (with synaptic vesicles and mitochondria)
2. The synaptic cleft (with basal lamina and acetylcholinesterase)
3. The postsynaptic muscle membrane (with infoldings.)
48
Where are nAChRs located at the NMJ, and what is their function?
* nAChRs are concentrated at the crests of secondary folds of the postsynaptic muscle membrane.
* Directly opposing the active zones of the presynaptic membrane.
49
What factors contribute to the plasticity of neuromuscular transmission?
- Involves the synthesis, storage, and release of acetylcholine, binding of acetylcholine to nicotinic receptors and action potential generation,
- Rapid hydrolysis of acetylcholine, and adaptation of muscle contractile proteins
50
How is synaptic plasticity defined?
* Is the ability of individual synaptic junctions to change in strength in response to either use or disuse.
51
How are synaptic vesicles (SVs) formed and transported to the nerve terminal?
* SVs are synthesized in the neuronal cell body within the endoplasmic reticulum
* Transported to the nerve terminal via the microtubule system.
52
How is acetylcholine loaded into SVs?
* Acetylcholine is synthesized from acetyl coenzyme A and choline.
* Then an energy-dependent transporter accumulates it within the vesicles, each containing 5,000 to 10,000 molecules.
53
What does a "quantum" of transmitter refer to in the context of SVs?
* Refers to the acetylcholine contained in a single vesicle.
54
What types of proteins are found in synaptic vesicles?
* Synaptic vesicles possess transport proteins for neurotransmitter uptake
* Proteins that mediate SV membrane traffic such as docking, fusion, and budding.
55
What are the two pools of vesicles in the nerve terminal?
1. There are two vesicle pools: a readily releasable store (active pool)
2. Reserve store. The active pool is aligned near the active zones.
56
What is the miniature endplate potential?
* Represents the depolarization produced by the contents of a single vesicle on the postsynaptic membrane.
57
How is the endplate potential generated?
* Results from the summation of miniature endplate potentials produced by the acetylcholine from fewer than 50 to 300 SVs.
58
What happens to acetylcholine after it is released from SVs?
* About 50% of released acetylcholine is hydrolyzed by acetylcholinesterase during diffusion across the synaptic cleft.
* Choline, a product of this hydrolysis, is recycled back into the terminal for acetylcholine resynthesis.
59
What is the synaptic cleft and its size?
* The synaptic cleft is a space less than 20 to 50 nm wide, separating nerve and muscle fiber plasma membranes.
* Encompasses the synaptic basal lamina, and filled with extracellular fluid.
60
What is the role of acetylcholinesterase at the synaptic cleft?
* Acetylcholinesterase, bound to the basal lamina at the cleft.
* Catalyzes the hydrolysis of acetylcholine, processing about 4,000 molecules per active site per second.
61
How efficient is acetylcholinesterase and where is it concentrated?
* Acetylcholinesterase is one of the most efficient catalytic enzymes.
* Is highly concentrated at the NMJ, with lower concentrations along muscle fibers.
62
Besides hydrolyzing acetylcholine, what other functions does acetylcholinesterase have?
* Has nerve growth-promoting activities.
* Modulates nicotinic acetylcholine receptors (nAChRs).
63
What factors regulate acetylcholinesterase?
* Is regulated by muscle activity and plasma membrane depolarization.
* Its density decreases significantly after denervation.
64
What is the structure and concentration of nAChRs in adult skeletal muscle?
* nAChRs are pentameric complexes concentrated at over 10,000 per μm² on the crests of junctional folds.
* Each with two α subunits and single β, δ, and ε subunits forming a transmembrane pore.
65
How do fetal and adult nAChRs differ?
* Fetal nAChRs contain a γ subunit instead of an ε subunit.
* Have a low conductance channel, shorter burst duration.
* Higher conductance to Na+, K+, and Ca2+ than adult nAChRs.
66
How does acetylcholine binding to nAChRs initiate channel opening?
* Binding of two acetylcholine molecules to the α subunits of nAChRs causes conformational changes, opening a channel for Na+ and Ca2+ influx and K+ efflux.
67
How do nondepolarizing neuromuscular-blocking drugs affect nAChRs?
* These drugs bind to one or both α subunits of nAChRs but lack agonist activity, preventing conformational changes.
* keeping the receptor channel closed, blocking neuromuscular transmission.
68
What is the effect of succinylcholine on nAChRs
* Succinylcholine, a partial agonist.
* Binds to the α subunit and opens ion channels.
* Causing a depolarizing block due to its prolonged channel opening as it is not hydrolyzed by acetylcholinesterase.
69
What happens when large doses of nondepolarizing neuromuscular-blocking drugs are used?
* High doses may enter nAChR channels, blocking ion flow and causing a blockade similar to that produced by local anesthetics on sodium ion channels.
70
Where do α motor neurons originate and how do they reach skeletal muscles?
- α Motor neurons originate from cell bodies in the brainstem or ventral horns of the spinal cord.
- Reach muscles through mixed peripheral nerves, with each nerve terminal innervating a single muscle cell.
71
What composes a motor unit?
* A single myelinated α motor neuron and all muscle fibers innervated by that neuron.
72
How do motor units vary in size and function?
- Larger motor nerves innervate more muscle fibers than smaller ones.
- Small units typically innervate red slow muscle fibers, while large units innervate white or pale fast muscle fibers.
73
What are the characteristics of red and white muscle fibers?
- Red muscle fibers (e.g., masseters) have high myoglobin, mitochondria, and capillary content and are resistant to fatigue.
- White muscle fibers (e.g., psoas muscle) have lesser such contents.
74
How does muscle fiber composition relate to muscle function?
- Muscles contain a mix of motor units, with the composition depending on their function.
- This mix determines the overall characteristics and capabilities of the muscle.
75
What are the three general classifications of muscle?
- Muscle is classified as skeletal, smooth, or cardiac.
- Both skeletal and cardiac muscles are striated, but they differ histologically and functionally.
76
What are the differences between skeletal and cardiac muscle cells?
- Skeletal muscle cells are multinucleated and tubular
- Cardiac muscle cells may be mono- or binucleated, are branched, and contain intercalated discs.
77
What are the primary functions of skeletal, smooth, and cardiac muscles?
- Skeletal muscle is responsible for voluntary actions, whereas
- Smooth and cardiac muscles are involved in cardiovascular, respiratory, gastrointestinal, and genitourinary system functions.
78
What percentage of total body mass is composed of muscle?
- Muscle composes 45% to 50% of total body mass,
- Skeletal muscles accounting for about 40% of body mass.
79
What is the specialization of muscle cells?
* Muscle cells are specialized for the conversion of chemical energy into mechanical energy.
80
How is smooth muscle activity related to certain illnesses?
* Inappropriate activity of smooth muscle is involved in illnesses such as hypertension, atherosclerosis, asthma, and gastrointestinal disorders.
