We evaluated the involvement of the sarcolemmal ATP-sensitive K+ channel in the depolarization of skeletal muscle fibers occurring in an animal model of human hypokalemic periodic paralysis, the K+-depleted rat. After 23-36 days of treatment with a K+-free diet, an hypokalemia was observed in the rats. No difference in the fasting insulinemia and glycemia was found between normokalemic and hypokalemic rats. The fibers of the hypokalemic rats were depolarized. In these fibers, the current of sarcolemmal ATP-sensitive K+ channels measured by the patch-clamp technique was abnormally reduced. Cromakalim, a K+ channel opener, enhanced the current and repolarized the fibers. At channel level, two open conductance states blocked by ATP and stimulated by cromakalim were found in the hypokalemic rats, The two states could be distinguished on the basis of their slope conductance and open probability and were never detected on muscle fibers of normokalemic rats. It is known that insulin in humans affected by hypokalemic periodic paralysis leads to fiber depolarization and provokes paralysis. We therefore examined the effects of insulin at macroscopic and single-channel level on hypokalemic rats. In normokalemic animals, insulin applied in vitro to the muscles induced a glybenclamide-sensitive hyperpolarization of the fibers and also stimulated the sarcolemmal ATP-sensitive K+ channels. In contrast, in hypokalemic rats, insulin caused a pronounced fiber depolarization and reduced the residual currents. Our data indicated that in hypokalemic rats, an abnormally low activity of ATP-sensitive K+ channel is responsible for the fiber depolarization that is aggravated by insulin.
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|Titolo:||The biophysical and pharmacological characteristics of skeletal muscle ATP-Sensitive K+ channels are modified in K+-depleted rat, an animal model of hypokalemic periodic paralysis|
|Data di pubblicazione:||1998|
|Citazione:||The biophysical and pharmacological characteristics of skeletal muscle ATP-Sensitive K+ channels are modified in K+-depleted rat, an animal model of hypokalemic periodic paralysis / Tricarico D; Pierno S; Mallamaci R; Brigiani GS; Capriulo R; Santoro G; Camerino DC. - In: MOLECULAR PHARMACOLOGY. - ISSN 0026-895X. - 54:1(1998), pp. 197-206.|
|Appare nelle tipologie:||1.1 Articolo in rivista|