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

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.