K+-dependent paradoxical membrane depolarization and Na+ overload, major and reversible contributors to weakness by ion channel leaks.

ABSTRACT: Normal resting potential (P1) of myofibers follows the Nernst equation, exhibiting about -85 mV at a normal extracellular K(+) concentration ([K(+)](o)) of 4 mM. Hyperpolarization occurs with decreased [K(+)](o), although at [K(+)](o) < 1.0 mM, myofibers paradoxically depolarize to a second stable potential of -60 mV (P2). In rat myofiber bundles, P2 also was found at more physiological [K(+)](o) and was associated with inexcitability. To increase the relative frequency of P2 to 50%, [K(+)](o) needed to be lowered to 1.5 mM. In the presence of the ionophore gramicidin, [K(+)](o) reduction to only 2.5 mM yielded the same effect. Acetazolamide normalized this increased frequency of P2 fibers. The findings mimic hypokalemic periodic paralysis (HypoPP), a channelopathy characterized by hypokal

SUBMITTER: Jurkat-Rott K 

PROVIDER: S-EPMC2644652 | biostudies-literature | 2009 Mar

REPOSITORIES: biostudies-literature