Insulin modulation of ATP-sensitive K+ channel of rat skeletal muscle is impaired in the hypokalaemic state

In the present work, we examined the effects of in vivo administration of i nsulin to rats made hypokalaemic by feeding a K+-free diet. The i.p. inject ion of insulin in the hypokalaemic rats provoked muscle paralysis within 3- 5 h. Consistent with this observation, the skeletal muscle fibres of the pa ralysed rats were depolarized. In contrast, in the normokalaemic animals, i nsulin neither provoked paralysis nor produced significant fibre hyperpolar ization. In the hypokalaemic rats, insulin almost completely abolished the sarcolemma adenosine triphosphate (ATP)-sensitive K+ currents without alter ing the sensitivity of the channels to ATP or glibenclamide. In contrast, i n the normokalaemic rats, insulin enhanced ATP-sensitive K+ currents that b ecame also resistant to ATP and glibenclamide. Our experiments indicate tha t the modulation of the sarcolemma ATP-sensitive K+ channels by insulin is impaired in the hypokalaemic state. This phenomenon appears to be related t o the fibre depolarization and paralysis observed in the same animals.