Adynamia episodica hereditaria with myotonia: A non‐inactivating sodium current and the effect of extracellular pH

TLDR

Normal muscle depolarizes to −63 mV in 9 mmol l⁻¹ K⁺ yet can generate full tetanic force. The study aimed to elucidate the mechanism of periodic paralysis in a patient with adynamia episodica hereditaria and myotonia by examining intact muscle fibers. Using voltage clamp on biopsied fibers at 3.5 mmol l⁻¹ K⁺, the authors identified a non‑inactivating inward sodium current activated below −80 mV that was TTX‑sensitive. The patient’s fibers exhibited a persistent, TTX‑sensitive inward sodium current that depolarized the muscle to −57 mV, rendering it inexcitable; lowering extracellular pH mitigated this effect, whereas hydrochlorothiazide had no in‑vitro benefit.

Abstract

Abstract To study the mechanism of periodic paralysis, we investigated the properties of intact muscle fibers biopsied from a patient who had adynamia episodica hereditaria with electromyographic signs of myotonia. When the potassium concentration in the extracellular medium, [K] e , was 3.5 mmol/l, force of contraction, membrane resting potential, and intracellular sodium activity were normal, but depolarizing voltage clamp steps revealed the existence of an abnormal inward current. This current was activated at membrane potentials less negative than −80 mV, reached a maximum within 50 msec, and was not inactivated with time. The inward current was completely and reversibly blocked by tetrodotoxin, which indicates that it was carried by sodium ions. In a solution containing 9 mmol/l potassium, normal muscle would depolarize to −63 mV and yet be capable of developing full tetanic force upon stimulation. The muscle from the patient depolarized to −57 mV and became inexcitable, i.e., it was paralyzed. A contracture did not develop. Lowering of the extracellular pH did not influence the resting potential, but it effectively antagonized or prevented the paralytic effect of high [K] e by changing the inactivation characteristics of the sodium channels. Hydrochlorothiazide, which had a therapeutic effect on the patient, did not prevent paralysis in vitro. An abnormal rise of the intracellular sodium activity was recorded when the extracellular potassium concentration was raised to 10 mmol/l.