Voltage dependence of ATP-dependent K+ current in rat cardiac myocytes is affected byI K1 andIK(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) -inducedI_K(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 ofI_K(ATP) was reduced at membrane potentials negative toE_K (around−50 mV), resulting in an outwardly rectifyingI–Vrelation. Overexpression of Kir2.1 by adenoviral gene transfer, a subunit contributing toI_K1 channels, in atrial myocytes resulted in a largeI_K1-like background current. TheI–Vrelation ofI_K(ATP) in these cells showed a reduced slope conductance negative toE_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-γ-S, theI–Vrelation ofI_K(ATP) showed a reduced slope negative toE_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 inwardI_K(ATP) and other inward rectifier currents in cardiac myocytes reflects steady-state changes in K⁺ driving force due to inward K⁺ current. [ABSTRACT FROM AUTHOR]