Physiology · Applied and Clinical Physiology Correlations (Pathophysiology Mechanisms)

A 45-year-old man presents with perioral numbness, carpopedal spasm, and positive Chvostek sign after thyroid surgery. Serum calcium is 7.2 mg/dL. Which physiological mechanism explains why a reduction in ionised calcium causes increased neuronal excitability?

  • A Hypocalcemia increases the resting membrane potential (makes it more positive), lowering the threshold for action potential firing
  • B Hypocalcemia directly depolarises nerve membranes by reducing the K+ equilibrium potential
  • C Low calcium inhibits the Na+/K+-ATPase, raising intracellular Na+ and depolarizing neurons
  • D Calcium normally stabilises voltage-gated Na+ channels in the inactivated state; low Ca2+ increases surface charge, lowers the activation threshold, and facilitates Na+ channel opening
Correct answer: D. Calcium normally stabilises voltage-gated Na+ channels in the inactivated state; low Ca2+ increases surface charge, lowers the activation threshold, and facilitates Na+ channel opening

Explanation

Extracellular Ca2+ binds to negative surface charges on the external face of voltage-gated Na+ channels, effectively shifting the voltage-activation curve rightward (requiring more depolarization to activate). When Ca2+ falls, this stabilizing effect is lost: the Na+ channel activation threshold shifts toward the resting membrane potential, making the neuron more excitable even at normal resting potential. This is the physicochemical basis of tetany and paresthesias in hypocalcemia — the membrane is not depolarized, but it is hair-trigger sensitive to minor stimuli.

Reference: Guyton & Hall, Textbook of Medical Physiology, 14th ed.

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