INTRINSIC GATING PROPERTIES OF A CLONED G-PROTEIN-ACTIVATED INWARD RECTIFIER K+ CHANNEL

The voltage-, time-, and K+-dependent properties of a G protein-activa ted inwardly rectifying K+ channel (GIRK1/KGA/Kir3.1) cloned from rat atrium were studied in Xenopus oocytes under two-electrode voltage cla mp. During maintained G protein activation and in the presence of high external K+ (V-K = 0 mV), voltage jumps from V-K to negative membrane potentials activated inward GIRK1 K+ currents with three distinct tim e-resolved current components. GIRK1 current activation consisted of a n instantaneous component that was followed by two components with tim e constants tau(f) similar to 50 ms and tau(s) similar to 400 ms. Thes e activation time constants were weakly voltage dependent, increasing approximately twofold with maximal hyperpolarization from V-K. Voltage -dependent GIRK1 availability, revealed by tail currents at -80 mV aft er long prepulses, was greatest at potentials negative to V-K and decl ined to a plateau of approximately half the maximal level at positive voltages. Voltage-dependent GIRK1 availability shifted with VK and was half maximal at V-K-20 mV; the equivalent gating charge was similar t o 1.6 e(-). The voltage-dependent gating parameters of GIRK1 did not s ignificantly differ for G protein activation by three heterologously e xpressed signaling pathways: m2 muscarinic receptors, serotonin 1A rec eptors, or G protein beta 1 gamma 2 subunits. Voltage dependence was a lso unaffected by agonist concentration. These results indicate that t he voltage-dependent gating properties of GIRK1 are not due to extrins ic factors such as agonist-receptor interactions and G protein-channel coupling, but instead are analogous to the intrinsic gating behaviors of other inwardly rectifying K+ channels.