Voltage dependence of ATP-dependent K+ current in rat cardiac myocytes is affected by IK1 and IK(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 I(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 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-V relation 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.
Department of Physiology, Ruhr-University Bochum, D-44780 Bochum, Germany.
Marie-Cécile
MC
Wellner-Kienitz
Kirsten
K
Bender
Andreas
A
Rinne
Lutz
L
Pott
D018528:ATP-Binding Cassette Transporters / Q000819:agonists / Q000502:physiology; D000109:Acetylcholine / Q000494:pharmacology*; D000255:Adenosine Triphosphate / Q000502:physiology*; D000818:Animals; D016466:CHO Cells; D002478:Cells, Cultured; D006224:Cricetinae; D051660:Intermediate-Conductance Calcium-Activated Potassium Channels; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000502:physiology*; D020110:Pinacidil / Q000494:pharmacology; D015221:Potassium Channels / Q000819:agonists / Q000502:physiology; D024681:Potassium Channels, Calcium-Activated / Q000819:agonists / Q000502:physiology; D024661:Potassium Channels, Inwardly Rectifying / Q000819:agonists / Q000502:physiology*; D051381:Rats; D011955:Receptors, Drug / Q000819:agonists / Q000502:physiology; D064233:Sulfonylurea Receptors; D000099161:Kcnj11 Channel
D018528:ATP-Binding Cassette Transporters; D000109:Acetylcholine; D000255:Adenosine Triphosphate; D051660:Intermediate-Conductance Calcium-Activated Potassium Channels; D020110:Pinacidil; D015221:Potassium Channels; D024681:Potassium Channels, Calcium-Activated; D024661:Potassium Channels, Inwardly Rectifying; D011955:Receptors, Drug; D064233:Sulfonylurea Receptors; D000099161:Kcnj11 Channel