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.