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PY3.1-12 | Nerve and Muscle Physiology — Part 3

Properties of Skeletal Muscle — Twitch, Tetanus & Length-Tension (PY3.9)

Individual muscle fibres obey the all-or-none law (like neurons), but whole muscles show graded contractions. Understanding how muscles grade their force is essential for clinical neuromuscular assessment.

The muscle twitch:
A single AP in a muscle fibre produces a single brief contraction — the twitch. It has three phases:
1. Latent period (~2 ms) — excitation-contraction coupling occurs; no visible tension yet
2. Contraction phase (~15-20 ms in fast fibres, ~75 ms in slow) — cross-bridges cycle, tension develops
3. Relaxation phase — SERCA pumps Ca²+ back into SR, cross-bridges release, tension falls

How the body grades muscle force:

1. Motor unit recruitment:
A motor unit = one motor neuron + all the muscle fibres it innervates. Small motor units (few fibres, e.g., 10 in extraocular muscles) are recruited first for fine control. Large motor units (thousands of fibres, e.g., in quadriceps) are recruited later for more force. This is the size principle (Henneman).

2. Frequency of stimulation — summation and tetanus:
• If a second stimulus arrives before the first twitch is complete, the tensions add — wave summation (temporal summation)
• As stimulus frequency increases: unfused (incomplete) tetanus → mechanical oscillations, average tension increases
• At high frequency: fused (complete) tetanus — smooth, sustained contraction at maximum tension (~4× the single twitch tension)
• The tetanic frequency is the minimum frequency for fused tetanus (~40-60 Hz for most muscles)

The length-tension relationship:
• At the optimal sarcomere length (~2.2 μm), there is maximum overlap between thick and thin filaments → maximum number of cross-bridges → maximum force
• If the muscle is stretched too far, thin filaments are pulled away from thick filaments → fewer cross-bridges → force decreases
• If the muscle is too short, thin filaments overlap each other and thick filaments are compressed against Z-lines → steric hindrance → force decreases
• The body keeps most muscles near their optimal length through joint anatomy and opposing muscle groups

Types of contraction:
• Isometric — muscle length stays the same, tension increases (e.g., holding a heavy object)
• Isotonic concentric — muscle shortens against a load (e.g., lifting a cup)
• Isotonic eccentric — muscle lengthens while producing tension (e.g., slowly lowering a cup)

Clinical significance: In a nerve conduction study + EMG, the physician stimulates the nerve at increasing frequencies and records the muscle response — checking for fatigue (decrement in myasthenia gravis) or facilitation (increment in Lambert-Eaton syndrome).

Smooth Muscle — A Different Machine (PY3.10)

Smooth muscle lines blood vessels, the GI tract, the urinary bladder, the uterus, and airways. It contracts slowly but can sustain contraction for very long periods — ideal for regulating blood flow, moving food, and maintaining organ tone.

Structure — how it differs from skeletal muscle:
• No sarcomeres — smooth muscle has no striations (hence 'smooth'). Actin and myosin are arranged in a criss-cross lattice anchored to dense bodies (analogous to Z-lines) and dense plaques on the cell membrane.
• No T-tubules — smooth muscle cells are small enough that Ca²+ from the surface and SR can reach the interior directly. Surface caveolae (small invaginations) function like primitive T-tubules.
• No troponin — smooth muscle uses a completely different regulatory mechanism (calmodulin, not troponin)
• Single nucleus — each smooth muscle cell is spindle-shaped with one central nucleus

Mechanism of contraction — the calmodulin pathway:
1. Ca²+ enters from outside (through L-type Ca²+ channels) and/or is released from the SR (via IP3 receptors, not ryanodine receptors)
2. Ca²+ binds calmodulin (not troponin C)
3. Ca²+-calmodulin activates myosin light chain kinase (MLCK)
4. MLCK phosphorylates the myosin light chain → myosin ATPase is activated → cross-bridge cycling begins
5. Relaxation: myosin light chain phosphatase (MLCP) dephosphorylates myosin → cross-bridges stop

The latch mechanism: Smooth muscle can maintain tension at very low energy cost. Even after Ca²+ falls and MLCK is deactivated, dephosphorylated cross-bridges detach very slowly — this 'latch state' lets blood vessels maintain tone without continuous energy expenditure.

Two types of smooth muscle:
• Multi-unit — each cell is separately innervated. Fine control. Examples: iris, ciliary muscle, vas deferens, piloerector muscles.
• Single-unit (visceral) — cells are connected by gap junctions and contract as a syncytium. Exhibits spontaneous rhythmic activity (slow waves). Examples: GI tract, uterus, ureter, small blood vessels.

Regulation: Smooth muscle is controlled by autonomic nerves (sympathetic and parasympathetic), hormones (oxytocin on uterus, angiotensin on blood vessels), local factors (NO, prostaglandins, stretch), and paracrine signals — NOT voluntary control.

Cardiac Muscle — Built for Endurance (PY3.11)

Cardiac muscle combines features of both skeletal and smooth muscle — it's striated (like skeletal) but involuntary (like smooth). It's uniquely adapted to beat continuously for a lifetime without fatigue.

Structure — what makes cardiac muscle unique:
• Striated — has sarcomeres with the same actin-myosin-troponin arrangement as skeletal muscle
• Short, branched cells — each with one or two central nuclei (vs. long multinucleated skeletal fibres)
• Intercalated discs — specialised junctions between cardiac cells containing:
- Desmosomes — mechanical anchoring (hold cells together)
- Gap junctions — electrical coupling (allow AP to spread from cell to cell as a functional syncytium)
• Abundant mitochondria — occupy ~25% of cell volume (vs. ~2% in skeletal muscle) — reflecting the heart's reliance on aerobic metabolism
• T-tubules present — wider than in skeletal muscle, located at Z-lines
• SR present but less developed than in skeletal muscle

Key differences from skeletal muscle:

Feature	Skeletal	Cardiac
Control	Voluntary	Involuntary (autorhythmic)
Innervation	Motor neuron (NMJ)	Autonomic (modulates, not initiates)
AP duration	1-2 ms	~200-300 ms (with plateau)
Refractory period	Short (~1-2 ms)	Long (~250 ms, nearly as long as the contraction)
Tetanus	Possible	IMPOSSIBLE (long refractory period prevents it)
Ca²+ source	Mainly SR (RyR1)	SR (RyR2) + extracellular (L-type Ca²+ channels)
E-C coupling	Mechanical (DHPR-RyR1 direct link)	Ca²+-induced Ca²+ release (CICR)

Ca²+-induced Ca²+ release (CICR):
In cardiac muscle, the AP opens L-type Ca²+ channels → a small amount of extracellular Ca²+ enters → this 'trigger Ca²+' opens RyR2 on the SR → a much larger Ca²+ release from the SR → contraction. This is fundamentally different from skeletal muscle where DHPRs are mechanically coupled to RyR1.

The long action potential and plateau phase:
The cardiac AP has 5 phases (0-4). The key difference is the plateau phase (Phase 2) — sustained by L-type Ca²+ channel influx balanced by K+ efflux. This plateau makes the AP last ~200-300 ms, and the long absolute refractory period that accompanies it prevents tetanus. This is essential — if the heart could tetanise, it would stop pumping blood and you would die.

Spiral forward: In Cardiovascular Physiology (PY5), you'll learn how the pacemaker cells (SA node, AV node) generate their own rhythmic APs — autorhythmicity — and how the conducting system (His bundle, Purkinje fibres) coordinates ventricular contraction.

Energy Metabolism of Muscle (PY3.12)

Muscle contraction requires enormous amounts of ATP. A sprinting athlete uses ATP 100× faster than at rest. Where does all this ATP come from?

Three energy systems, in order of speed:

1. Phosphocreatine (PCr) system — immediate energy (first 8-10 seconds)
• Creatine kinase transfers a phosphate from phosphocreatine to ADP → ATP
• PCr + ADP → Cr + ATP (reversible, catalysed by creatine kinase)
• Fastest source, but very limited stores (~5 mM in muscle)
• Fuels: a single sprint, a heavy lift, the first few seconds of any intense effort
• Clinical: Serum creatine kinase (CK) is elevated in muscle damage (MI, rhabdomyolysis, muscular dystrophies) — it leaks from damaged muscle cells

2. Anaerobic glycolysis — short-term energy (10 seconds to 2 minutes)
• Glucose (from blood or muscle glycogen) is broken down to pyruvate → lactate
• Produces 2 ATP per glucose (net) — fast but inefficient
• Does NOT require oxygen
• Fuels: intense efforts lasting up to ~2 minutes (400m sprint, weightlifting sets)
• Limitation: lactate accumulation → pH drops → inhibits phosphofructokinase and other enzymes → fatigue

3. Aerobic oxidative phosphorylation — sustained energy (2 minutes onwards)
• Substrates: glucose, fatty acids, (and amino acids during prolonged exercise)
• Pyruvate enters mitochondria → acetyl-CoA → TCA cycle → electron transport chain → 36-38 ATP per glucose
• Fatty acids: β-oxidation → acetyl-CoA → even more ATP per molecule (e.g., palmitate → ~129 ATP)
• Requires oxygen — dependent on cardiovascular delivery (cardiac output, blood flow, haemoglobin)
• Fuels: all activities lasting more than ~2 minutes (walking, jogging, marathon running)

Oxygen debt (Excess Post-Exercise Oxygen Consumption — EPOC):
After intense exercise, you continue breathing heavily for minutes — this is your body repaying the 'oxygen debt':
• Alactacid component — oxygen used to re-synthesise phosphocreatine and replenish myoglobin O₂ stores (~2-3 minutes)
• Lactacid component — oxygen used to convert lactate back to glucose in the liver (Cori cycle) and to fuel the elevated metabolic rate (~30-60 minutes)

Muscle fatigue:
Fatigue is the progressive decline in muscle force during sustained activity. It's multifactorial:
• Peripheral factors — accumulation of Pi (from ATP hydrolysis, the main culprit), H+ (from lactate), K+ (in the T-tubules), depletion of glycogen
• Central factors — reduced motor cortex drive, reduced motivation
• Fatigue is a protective mechanism — it prevents muscle damage from excessive energy depletion

Biochemistry link: In BI (Minerals and Electrolytes), you're learning about the ions (Ca²+, Na+, K+) and cofactors that power these metabolic pathways. The ATP that fuels every cross-bridge cycle comes from the very metabolic pathways you study in Biochemistry.