7.2 Muscle Physiology

Why muscle physiology is a scored Physiology topic

Muscle physiology is 12% of the Physiology domain (Physiology is 18% of Part I). Official bullets are cardiac muscle, skeletal muscle, and smooth muscle. Anatomy already named compartments and sarcomere histology; this section is control of force: how an action potential becomes cross-bridges, why skeletal muscle can tetanize and cardiac muscle cannot, and how smooth muscle holds tone cheaply.

A chiropractic-relevant hook is the spindle versus Golgi-tendon-organ pairing from neurophysiology: spindles sit in parallel and see length; tendon organs sit in series and see tension. The contractile machinery below is what those receptors are reporting.

Skeletal muscle: neuromuscular junction

A motor unit is one alpha motor neuron plus every extrafusal fiber it innervates. Extraocular and intrinsic-hand units are small; gluteus maximus units are large.

The axon terminal lies in a synaptic gutter packed with nicotinic acetylcholine receptors (adult pentamers, two α subunits bind acetylcholine). Arrival of a spike opens P/Q-type Ca2+ channels; vesicles fuse; acetylcholine diffuses ~50 nm. Binding opens the nicotinic channel (Na+ in, K+ out, reversal near 0 mV). The end-plate potential is typically ~40 mV—far above the ~15 mV needed to fire a sarcolemmal spike. That safety factor is why a healthy junction does not fail during ordinary tetanus. Acetylcholinesterase in the basal lamina hydrolyzes acetylcholine so the end plate can repolarize before the next impulse.

Curare-like nicotinic antagonists shrink the end-plate potential and can drop it below threshold. Acetylcholinesterase inhibitors enlarge and prolong it (useful in myasthenia, dangerous as depolarizing block if excessive). Depolarizing blockers (succinylcholine) open the receptor and keep the end plate depolarized so Na+ channels inactivate. Botulinum cuts SNAREs and stops vesicle fusion; Lambert–Eaton cuts presynaptic Ca2+ entry; myasthenia cuts receptor number. Three failure points, three different frequency patterns.

Skeletal excitation–contraction coupling

The sarcolemmal spike races into T-tubules that invaginate at the A–I junction. Each T-tubule plus two sarcoplasmic-reticulum terminal cisternae is a triad. The T-tubule dihydropyridine receptor (DHPR, Cav1.1) is a voltage sensor. In skeletal muscle it is mechanically linked to ryanodine receptor type 1 (RyR1) on the sarcoplasmic reticulum. Depolarization opens RyR1; stored Ca2+ floods the cytosol (from ~10^−7 M toward ~10^−5 M).

Ca2+ binds troponin C. Troponin I inhibition lifts; tropomyosin rolls off myosin-binding sites on actin. Cross-bridges cycle until SERCA (sarcoplasmic/endoplasmic reticulum Ca2+-ATPase) pumps Ca2+ back into the reticulum, helped by calsequestrin buffering inside the store. Malignant hyperthermia is a leaky RyR1: uncontrolled Ca2+ release, sustained contraction, heat, and rigidity. Dantrolene stabilizes RyR1.

Cross-bridge cycle, length–tension, and force–velocity

ATP is the allosteric key, not a sticky glue:

1. ATP binds myosin → myosin detaches from actin (no ATP = rigor).
2. Hydrolysis to ADP + Pi cocks the head.
3. Weak binding to actin; Pi release → power stroke.
4. ADP release; the head stays attached until the next ATP binds.

Each cycle hydrolyzes one ATP per head. Force is proportional to the number of attached bridges in the force-generating states.

Length–tension. Thick–thin overlap is maximal at sarcomere lengths of about 2.0–2.2 μm. Stretch beyond that reduces overlap and force. Extreme shortening causes double overlap and thick-filament collision with Z discs—force falls. Passive tension from titin and connective tissue rises steeply at long lengths. The same curve, applied to the ventricle, is the cellular basis of Frank–Starling (below).

Force–velocity (Hill). Unloaded shortening velocity (Vmax) is set by myosin ATPase isoform (fast fibers have higher Vmax). Isometric force (velocity = 0) is Fmax, set by overlap and activation. Power peaks at intermediate loads. You cannot have maximal force and maximal velocity at the same instant.

Fiber types, twitch, and tetanus

A single spike produces a twitch: Ca2+ is resequestered before force fully develops. If a second spike arrives before relaxation, cytosolic Ca2+ and force summate. High-frequency stimulation fuses twitches into unfused, then fused tetanus. Skeletal muscle can tetanize because the action potential and refractory period (~1–5 ms) are much shorter than the twitch (~20–100+ ms depending on fiber type). Treppe (staircase) is a separate, slower rise in twitch force with repeated stimulation from better SR loading and Ca2+ sensitivity—not the same as tetanic summation.

Motor-unit recruitment still follows the size principle: posture first (type I), then type II as demand rises. Training adaptations (mitochondrial density, fiber-type shifts) are expanded in exercise physiology; the exam still expects you to match fiber biochemistry to function here.

Cardiac muscle

Ventricular myocytes are striated, branched, and electrically coupled by gap junctions (connexin 43) at intercalated discs, so the ventricle is a functional syncytium. They have diads (one T-tubule plus one cisterna at the Z line), not skeletal triads. They lack satellite-cell repair.

Plateau action potential (ventricular myocyte)

Duration is about 200–400 ms—two orders of magnitude longer than a neuronal spike. That long refractory period is why cardiac muscle cannot tetanize: the mechanical twitch is over before another spike can be triggered. Summation would be fatal in a pump that must fill.

Pacemaker cells lack a stable phase 4 and use a different upstroke (next section). Absolute (effective) refractory period spans most of the plateau because Na+ channels remain inactivated until Vm repolarizes. A premature stimulus in the relative refractory period can trigger a poorly propagating action potential—the physiology behind some reentrant arrhythmias, without turning this into a Part III ECG course.

Calcium-induced calcium release

Cardiac DHPR is Cav1.2. It is not a mechanical wrench on the ryanodine receptor. During the plateau, a modest L-type Ca2+ current enters; that trigger Ca2+ opens RyR2 on the sarcoplasmic reticulum (calcium-induced calcium release, CICR). Amplification is large: most of the Ca2+ that binds troponin C came from the store, not from the trigger current. Relaxation requires SERCA (regulated by phospholamban) plus Na+/Ca2+ exchange (NCX) to extrude the trigger Ca2+ that entered through Cav1.2. If NCX fails to match entry, the cell gains Ca2+.

β1-adrenergic stimulation (Gs → cAMP → protein kinase A) phosphorylates L-type channels (more trigger Ca2+ → inotropy), RyR2 (more release), and phospholamban (relieves SERCA inhibition → faster reuptake → lusitropy, more filling time and a fuller store for the next beat). That is why sympathetic drive raises both contractility and relaxation rate. Cardiac glycosides inhibit Na+/K+ ATPase, raise intracellular Na+, slow NCX Ca2+ extrusion, and raise store content—positive inotropy by a different route.

Frank–Starling relationship

Within physiologic limits, increased ventricular end-diastolic fiber length increases stroke volume. The mechanism is length-dependent activation: more optimal actin–myosin overlap plus increased Ca2+ sensitivity of troponin C (and stretch-related changes in Ca2+ handling). It is not a change in contractility. Contractility (inotropy) is a load-independent shift of the entire Starling curve (catecholamines, digitalis, loss of myocardium). Preload is the stretch (end-diastolic volume or pressure). Afterload is the load during ejection (aortic pressure; more precisely wall stress).

Typical rest numbers: end-diastolic volume about 120 mL, end-systolic volume about 50 mL, stroke volume about 70 mL, ejection fraction about 55–70%. Matching right and left stroke volumes beat-to-beat is Frank–Starling's job when venous return wobbles. Isolated skeletal muscle has the same length–tension curve; the heart uses it as a pump law.

Smooth muscle

Smooth muscle has no sarcomeric striations, no troponin, and often no T-tubules. Thin filaments use caldesmon and calponin. Thick filaments are side-polar, so the cell can shorten over a wide length range and still make force—useful in a bladder or uterus.

Activation. A rise in cytosolic Ca2+ (from voltage-gated Ca2+ channels, IP3-gated sarcoplasmic reticulum, or store-operated entry) binds calmodulin. The Ca2+–calmodulin complex activates myosin light-chain kinase (MLCK). MLCK phosphorylates the regulatory myosin light chain (MLC20, serine 19). Phosphorylated myosin can bind actin and cycle. Relaxation: Ca2+ falls, MLCK quiets, and myosin light-chain phosphatase (MLCP) dephosphorylates myosin.

Latch. After phosphorylation has fallen, some dephosphorylated myosin heads remain attached to actin and decay slowly. Force is maintained at a low ATP cost. That is the latch state—how a vessel or sphincter holds tone without fatiguing like tetanic skeletal muscle. Rho kinase inhibits MLCP, raising force at a given Ca2+ (Ca2+ sensitization). Pharmacomechanical coupling can change force via IP3 and Rho kinase without a change in membrane potential. Electromechanical coupling uses depolarization and L-type Ca2+ entry.

Vascular smooth muscle mixes both. Local metabolites and endothelium (nitric oxide → cGMP → MLCP-favoring relaxation) dominate many beds; that story continues under circulation.

Three-muscle comparison (the exam table)

If a stem gives you a plateau, CICR, and Frank–Starling, it is cardiac. If it gives you DHPR–RyR1 mechanical coupling and fused tetanus, it is skeletal. If it gives you MLCK, calmodulin, and latch, it is smooth.