Effect of acidosis on transient outward potassium current in isolated rat ventricular myocytes

The effect of acidosis on the transient outward K+ current (I-to) of rat ve ntricular myocytes has been investigated using the perforated patch-clamp t echnique. When the holding potential was -80 mV, depolarizing pulses to pot entials positive to -20 mV activated I-to in subepicardial cells but activa ted little I-to in subendocardial cells. Exposure to an acid solution (pH 6 .5) had no significant effect on I-to activated from this holding potential in either subepicardial or subendocardial cells. When the holding potentia l was -40 mV, acidosis significantly increased It, at potentials positive t o -20 mV in subepicardial cells but had little effect on I-to in subendocar dial cells. The increase in I-to in subepicardial cells was inhibited by 10 mM 4-aminopyridine. In subepicardial cells, acidosis caused a +8.57-mV shi ft in the steady-state inactivation curve. It is concluded that in subepica rdial rat ventricular myocytes acidosis increases the amplitude of I-to as a consequence of a depolarizing shift in the voltage dependence of inactiva tion.