Voltage dependence of ATP-dependent K+ current in rat cardiac myocytes is affected by /K1 and /K(ACh)

In this study we have investigated the voltage dependence of ATP-dependent K+ current (I-K(ATP)) in atrial and ventricular myocytes from hearts of adult rats and in CHO cells expressing Kir6.2 and SUR2A. The current-voltage relation of 2,4-dinitrophenole (DNP) -induced IK(ATP) in atrial myocytes and expressed current in CHO cells was linear in a voltage range between 0 and -100 mV. In ventricular myocytes, the background current-voltage relation of which is dominated by a large constitutive inward rectifier (I-K1), the slope conductance of I-K(ATP) was reduced at membrane potentials negative to E-K (around - 50 mV), resulting in an outwardly rectifying I-V relation. Overexpression of Kir2.1 by adenoviral gene transfer, a subunit contributing to I-K1 channels, in atrial myocytes resulted in a large I-K1-like background current. The I-V relation of I-K(ATP) in these cells showed a reduced slope conductance negative to E-K similar to ventricular myocytes. In atrial myocytes with an increased background inward-rectifier current through Kir3.1/Kir3.4 channels (I-K(ACh)), irreversibly activated by intracellular loading with GTP-gamma-S, the I-Vrelation of I-K(ATP) showed a reduced slope negative to E-K, as in ventricular myocytes and atrial myocytes overexpressing Kir2.1. It is concluded that the voltage dependencies of membrane currents are not only dependent on the molecular composition of the charge-carrying channel complexes but can be affected by the activity of other ion channel species. We suggest that the interference between inward I-K(ATP) and other inward rectifier currents in cardiac myocytes reflects steady-state changes in K+ driving force due to inward K+ current.