THE BIOPHYSICAL AND PHARMACOLOGICAL CHARACTERISTICS OF SKELETAL-MUSCLE ATP-SENSITIVE K-DEPLETED RAT, AN ANIMAL-MODEL OF HYPOKALEMIC PERIODIC PARALYSIS( CHANNELS ARE MODIFIED IN K+)

We evaluated the involvement of the sarcolemmal ATP-sensitive K+ chann el in the depolarization of skeletal muscle fibers occurring in an ani mal model of human hypokalemic periodic paralysis, the K+-depleted rat . After 23-36 days of treatment with a K+-free diet, an hypokalemia wa s observed in the rats. No difference in the fasting insulinemia and g lycemia was found between normokalemic and hypokalemic rats. The fiber s of the hypokalemic rats were depolarized. In these fibers, the curre nt of sarcolemmal ATP-sensitive K+ channels measured by the patch-clam p technique was abnormally reduced. Cromakalim, a K+ channel opener, e nhanced the current and repolarized the fibers. At channel level, two open conductance states blocked by ATP and stimulated by cromakalim we re found in the hypokalemic rats, The two states could be distinguishe d on the basis of their slope conductance and open probability and wer e never detected on muscle fibers of normokalemic rats. It is known th at 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 hypo kalemic rats. In normokalemic animals, insulin applied in vitro to the muscles induced a glybenclamide-sensitive hyperpolarization of the fi bers and also stimulated the sarcolemmal ATP-sensitive K+ channels. In contrast, in hypokalemic rats, insulin caused a pronounced fiber depo larization and reduced the residual currents. Our data indicated that in hypokalemic rats, an abnormally low activity of ATP-sensitive K+ ch annel is responsible for the fiber depolarization that is aggravated b y insulin.