Activation of ATP-sensitive K channels by a K channel opener (SR 44866) and the effect upon electrical and mechanical activity of frog skeletal muscle.

Abstract

To examine the effects of the activation of adenosine 5'-triphosphate (ATP)-sensitive K channels in a skeletal muscle we have applied the ATP-sensitive K channel opener SR44866 whilst recording single ion channels, voltage-clamped membrane currents, evoked action potentials and tension in sartorius muscles of the frog. In excised inside-out membrane patches SR44866 opened channels which could be inhibited by internal ATP and glibenclamide. In voltage-clamped individual muscle fibres SR44866 evoked a glibenclamide-sensitive membrane current which reversed at -70 mV. The effect of SR44866 was dose dependent with an effective concentration for 50% maximal effect (EC50) of 67 microM and a slope factor of 2. SR44866 dose dependently reduced the duration of the spike after-potential, spike overshoot, Vmax, tetrodotoxin-sensitive voltage-gated inward membrane currents and muscle twitch tension. From this evidence it can be concluded that the opening of ATP-sensitive K channels may be associated with the inhibition of contraction of skeletal muscle.