SR47063, a potent channel opener, activates KATP and a time-dependent current likely due to potassium accumulation

(i) We studied the effects of a new cromakalim analogue, SR47063, in guinea-pig ventricular cells. The experiments were carried out in whole-cell patch clamp with internal and external solutions supposedly similar to the physiological ones. (ii) SR47063 reversibly activated a time-independent current reversing near the potassium equilibrium potential, and a time-dependent current reversing at a more positive potential. Both currents were blocked by application of glibenclamide. (iii) The time-independent and the time-dependent currents were activating for the same concentration of agonist in every cell, this concentration being very different from cell to cell. (iv) The amplitude of the time-dependent current was shown to depend directly neither on agonist concentration nor on potential, but rather on the amplitude of the current flowing during the prepulse before the test pulse. (v) We conclude that SR47063 is a potent KATP channel opener acting at concentrations lower than one micromolar, and that the time-dependent current is likely due to accumulation and depletion of potassium in restricted areas of the cells.