Inactivation of I(A) channels of frog skeletal muscle is modulated by ATP

Whole cell, voltage clamp experiments were performed in vesicles derived from frog skeletal muscle plasma membranes to characterize the influence of ATP on the kinetic properties of fast inactivating K(+) currents (I(A)). I(A) was recorded in ATP-free solutions. Peak I(A) decayed with a time constant of 27 ms at large depolarizations. Steady state inactivation reached half maximal values at -66 mV. In the presence of ATP, these values were 196 ms and -41 mV, respectively, indicating a major effect of ATP on inactivation. In contrast, activation of I(A) was unaffected by ATP. The protein kinase C (PKC) inhibitors, H7 and staurosporine, greatly prevented the effects of ATP on inactivation. Inactivation remained unchanged by the protein kinase A inhibitor HA1004 or by the catalytic subunit of cAMP protein kinase. We conclude that ATP decreases inactivation of skeletal muscle I(A) and that this effect may be mediated by protein kinase C.