ISOPROTERENOL-INDUCED AND INSULIN-INDUCED HYPERPOLARIZATION IN RAT SKELETAL-MUSCLE

Using conventional microelectrode techniques, we investigated the comb ined effects of isoproterenol (Iso) and insulin (Ins) on the resting m embrane potential (RMP) of isolated rat skeletal muscles. In soleus mu scle, Iso (1 muM) and Ins (4 units/L) separately induced a hyperpolari zation of 9.2 mV and 4.8 mV, respectively. Combined administration of Iso and Ins induced a hyperpolarization of 12.4 mV, larger than either one separately. A similar observation was made in Na+-loaded rewarmin g experiments. 8-Br-cAMP (1 mM and 3 mM) and forskolin (10 muM, an ade nylate cyclase activator) induced a hyperpolarization of 5.3 mV, 8 mV, and 6.0 mV, respectively. This hyperpolarizing action was blocked by ouabain, indicating that the Na-K pump was involved in the hyperpolari zation. 8-Br-cGMP (3 mM) had no effect on RMP; however, it blocked or reversed the hyperpolarization caused by 8-Br-cAMP (1 mM). In addition , 8-Br-cGMP partially inhibited the hyperpolarizing effect of Iso (1 m uM) by 40% and completely prevented the effect of Ins. The phorbol est er, PMA, (1 muM, a PKC activator) induced a ouabain-inhibitable hyperp olarization. These results suggest that cAMP and PKC are involved in t he Iso- and Ins-induced hyperpolarization and that Iso and Ins influen ce the RMP presumably through regulation of the electrogenic Na-K pump via different mechanisms. (C) 1993 Wiley-Liss, Inc.