Nerve & Muscle Physiology NP

An action potential is a regenerative change in membrane conductance. Rapid depolarization commonly reflects inward current through voltage-gated channels; repolarization follows channel inactivation and increased outward conductance. Refractory periods impose directionality and limit firing frequency.

Distinguish local graded potentials from all-or-none regenerative action potentials. Conduction velocity rises with axon diameter and myelination.

Demyelination slows or blocks conduction; electrolyte and channel disorders alter excitability.

Action-potential amplitude does not encode stimulus strength in the same way a graded potential does; frequency and recruitment carry much of the information.

At chemical synapses, presynaptic depolarization opens calcium channels, calcium triggers vesicle fusion, transmitter crosses the cleft and binds postsynaptic receptors. Excitatory and inhibitory inputs are integrated spatially and temporally.

Track information from presynaptic voltage to calcium entry to transmitter release to postsynaptic conductance.

Neuromuscular blockers, toxins and receptor disorders illustrate how failure at one synaptic step produces weakness or paralysis.

A neurotransmitter is not inherently excitatory or inhibitory; the receptor and ion conductance determine the postsynaptic effect.

Motor-neuron activity produces a muscle action potential that travels along sarcolemma and T tubules. Excitation activates calcium release from sarcoplasmic reticulum; calcium binds troponin, allowing actin-myosin cycling. ATP is required for cross-bridge cycling and calcium reuptake.

Link electrical excitation → calcium signal → regulatory-protein movement → cross-bridge cycle → force → relaxation.

Disorders of neuromuscular transmission, calcium handling or contractile proteins can produce weakness, fatigue or rigidity.

ATP is needed not merely for contraction but also for detachment of myosin and restoration of calcium gradients.

Smooth muscle lacks the skeletal-muscle troponin switch and uses calcium-calmodulin activation of myosin light-chain kinase. Contraction can be initiated by autonomic nerves, hormones, local factors or stretch.

Compare regulatory strategy rather than memorizing isolated differences: skeletal muscle mainly regulates actin accessibility; smooth muscle prominently regulates myosin phosphorylation.

Vascular, airway, gastrointestinal and uterine smooth muscle are major therapeutic targets.

Smooth muscle can maintain force economically through latch-like states and does not require the same striated architecture as skeletal muscle.

Excitable membranes convert physical or chemical stimuli into electrical signals. A local stimulus first produces a graded change in membrane potential. Graded potentials vary with stimulus strength and can summate. If depolarization at the trigger region reaches threshold, voltage-gated channels generate a regenerative action potential whose amplitude is relatively stereotyped. Stronger stimuli are therefore commonly represented by changes in firing frequency and recruitment rather than by progressively larger action potentials.

Propagation occurs because local current from an active membrane region depolarizes the next region to threshold. The refractory state behind the advancing impulse makes immediate re-excitation difficult and helps preserve forward propagation. Myelination and axon diameter determine how rapidly this electrical information travels.

Clinical reasoning: demyelination, local anaesthetics, electrolyte disturbances and channelopathies can impair conduction by different mechanisms. The student should identify whether the problem changes threshold, channel availability, membrane insulation or the electrochemical gradient.

Teach it back: explain why a stronger sensory stimulus can feel stronger even though individual action potentials remain approximately all-or-none.

When an action potential reaches a presynaptic terminal, depolarization opens voltage-gated calcium channels. Calcium entry increases vesicle fusion and neurotransmitter release. Transmitter diffuses across the synaptic cleft and binds postsynaptic receptors, changing ion conductance or intracellular signalling. The resulting postsynaptic potential may be excitatory or inhibitory depending on the receptor and ions involved.

At the neuromuscular junction, motor-neuron acetylcholine activates nicotinic receptors on skeletal muscle, producing an end-plate potential. If threshold is reached, a muscle action potential propagates across the sarcolemma and into T tubules. Acetylcholinesterase limits transmitter action, allowing precise repeated signalling.

Clinical reasoning: weakness can arise before the muscle contractile machinery itself is damaged. Reduced transmitter release, receptor blockade, receptor loss or impaired action-potential generation can all interrupt the nerve-to-muscle chain.

Teach it back: trace one motor-neuron action potential from the nerve terminal to generation of a skeletal-muscle action potential.

The skeletal-muscle action potential travels through T tubules, where voltage-sensitive proteins communicate with calcium-release channels in the sarcoplasmic reticulum. Cytosolic calcium rises and binds troponin C. The troponin-tropomyosin complex changes position, exposing actin sites so myosin heads can form cross-bridges and generate force.

ATP has several essential roles. ATP binding permits myosin to detach from actin; ATP hydrolysis energizes the myosin head for another cycle; ATP-dependent pumps return calcium to the sarcoplasmic reticulum so relaxation can occur. Thus ATP is required for both effective cycling and restoration of the resting state. Without ATP, persistent actin-myosin attachment contributes to rigor.

Force depends on the number and behaviour of active cross-bridges and on muscle length, stimulation pattern and motor-unit recruitment. Repeated stimuli can summate mechanically because cytosolic calcium remains elevated between closely spaced action potentials.

Teach it back: explain why electrical excitation can finish before mechanical tension has completely disappeared.

Smooth muscle uses actin and myosin but does not regulate contraction with the skeletal-muscle troponin system. Calcium binds calmodulin, which activates myosin light-chain kinase; phosphorylation of myosin promotes cross-bridge interaction. Relaxation involves reduced calcium signalling and myosin dephosphorylation.

Smooth muscle can be activated by autonomic nerves, hormones, local mediators, stretch and spontaneous electrical activity. This flexibility allows vascular, gastrointestinal, airway and uterine smooth muscle to behave differently according to organ function. Some smooth muscle can maintain force with low energy expenditure through latch-like cross-bridge behaviour.

Clinical reasoning: drugs that alter calcium entry, receptor signalling or myosin phosphorylation can change vascular resistance, airway calibre or gastrointestinal motility.

Teach it back: compare the calcium-dependent regulatory switch in skeletal muscle with that in smooth muscle.