Week 10 Study Guide

Presynaptic cell vs postsynaptic cell

Presynaptic cell sends the signal; postsynaptic cell receives the signal

What is the synaptic terminal bouton?

The swollen end of the axon where neurotransmitter is released

What is the synaptic cleft?

The small gap between the presynaptic and postsynaptic cells

Core steps of chemical synaptic transmission

AP arrives → bouton depolarizes → Ca2+ channels open → Ca2+ enters → vesicles fuse → neurotransmitter released → binds receptors → postsynaptic potential changes → neurotransmitter removed

What opens in the presynaptic bouton when an action potential arrives?

Voltage-gated Ca2+ channels

What directly triggers vesicle fusion?

Ca2+ influx into the bouton

Three ways neurotransmitter is removed

Reuptake, enzymatic degradation, diffusion

What is nAChR?

A ligand-gated nonselective cation channel activated by acetylcholine

What ions move through nAChR?

Na+ in and K+ out

Net effect of opening nAChR

Depolarization due to greater Na+ influx than K+ efflux

Why does nAChR depolarize (GHK logic)?

Increased Na+ permeability shifts Vm toward ENa, making it less negative

What is the NMJ?

The synapse between a motor neuron and skeletal muscle

What is the motor end plate?

Region of muscle membrane with nicotinic receptors

Neurotransmitter at NMJ

Acetylcholine

Muscle structure hierarchy

Muscle → fascicle → muscle fiber → myofibril → sarcomere → myofilaments

Series vs parallel arrangement

Sarcomeres in series; myofibrils in parallel

What is the sarcolemma?

The membrane of a muscle fiber

What is a sarcomere?

The repeating contractile unit

Thick vs thin filaments

Thick = myosin; thin = actin + troponin + tropomyosin

Actin, myosin, troponin, tropomyosin roles

Actin binds myosin; myosin is motor protein; troponin binds Ca2+; tropomyosin blocks binding sites

Excitation in muscle

ACh → nAChR opens → depolarization → muscle AP via Na+ channels → spreads through sarcolemma/T-tubules

Coupling in muscle

AP activates DHP → activates RyR → Ca2+ released from SR

How is Ca2+ returned to SR?

By SERCA pump using ATP

Effect of Ca2+ presence vs absence

No Ca2+ = no contraction; Ca2+ present = binding sites exposed → contraction

Cross-bridge step 1

Myosin binds actin (attachment)

Cross-bridge step 2

Power stroke: myosin pulls actin; ADP + Pi released

Cross-bridge step 3

ATP binds → myosin detaches

Cross-bridge step 4

ATP hydrolyzed → myosin recocks

Role of ATP binding

Causes myosin detachment

Role of ATP hydrolysis

Re-cocks myosin head

Full contraction sequence

Motor neuron AP → Ca2+ entry → ACh release → nAChR opens → muscle AP → SR Ca2+ release → troponin binds Ca2+ → cross-bridge cycling → shortening

Relaxation sequence

Motor neuron stops → ACh degraded → Ca2+ pumped into SR → tropomyosin blocks actin → relaxation

Effect of ATP depletion

Rigor; myosin cannot detach

Effect of Ca2+ removal

Contraction stops → relaxation

ACh agonist effect

Continuous depolarization → spastic contraction

ACh antagonist effect

Blocks contraction → flaccid paralysis

AChE inhibitor effect

Prolonged ACh → sustained contraction

Sarin effect

AChE inhibitor → depolarization → full contraction

Nicotine effect

nAChR agonist → depolarization → full contraction

Tetrodotoxin effect

Blocks Na+ channels → no muscle AP → relaxation

Flaccid paralysis definition

Inability to contract

Spastic paralysis definition

Inability to relax

Rigor definition

Stuck contraction due to no ATP

Block ADP/Pi release effect

Stuck in power stroke (step 2)

Remove Ca2+ effect on cycle

Myosin stuck detached (step 4)

Block ATP hydrolysis effect

Cannot recock; stuck detached

Block ATP binding effect

Myosin stuck attached (rigor-like)

Effect of myosin mutation

Poor thick filament formation → fewer cross-bridges → muscle weakness

Sliding filament theory

Filaments slide past each other; they do not shorten

Band changes during contraction

Z disks closer; H zone and I band shrink; A band unchanged

High-energy myosin state

Cocked conformation after ATP hydrolysis

Myosin state without Ca2+

Cocked but cannot bind actin

How ACh triggers Ca2+ release

ACh → AP → T-tubules → SR Ca2+ channels open

Why skeletal muscle is not autonomic target

Controlled by somatic motor neurons only

nAChR ion selectivity

Cation-specific but nonselective (Na+ and K+)

Receptor types summary

Nicotinic and muscarinic bind ACh; adrenergic bind NE/epinephrine

Longest-lasting event in muscle twitch

Cross-bridge cycling

Smallest contraction scenario

One AP in largest motor unit only

Structure order (largest → smallest)

Fascicle → muscle cell → myofibril → sarcomere

Power stroke event

Release of ADP and Pi

ATP’s main role

Provides energy to re-cock myosin

What Sarin does NOT increase

Motor neuron firing rate

Effect of nAChR antagonist on ion flux

Decreases both Na+ and K+ flux