Inwardly rectifying K+ currents of alveolar type II cells isolated from fetal guinea-pig lung: regulation by G protein- and Mg2+-dependent pathways.

K+ currents in alveolar type II cells, isolated from fetal guinea-pig lung, were studied using the whole-cell patch-clamp technique. Inwardly rectifying (IR) K+ currents were observed when cells were bathed in symmetrical KCl-rich solutions. When extracellular K+ was replaced by Na+, inward currents were greatly decreased and the zero-current potential moved from 0 mV to -69 mV, indicating high K+ selectivity. In recordings with an intracellular KCl-rich solution, containing 1.12 mM Mg2+ and 10(-8 )M free Ca2+, IR K+ currents slowly diminished with time. Addition of the irreversible G protein activator, guanosine 5'-O-(3-thiotriphosphate) (GTP [gamma-S]), to the intracellular solution accelerated the rate of current run-down. In experiments where the intracellular solution was Mg2+ free, current run-down was abolished. The rate of current run-down was found to increase with increasing free intracellular [Mg2+]. Raising the intracellular free [Ca2+] to 10(-6 )M under Mg2+-free conditions had no effect on the K+ currents. Extracellular Ba2+ blocked the IR K+ currents in a concentration- and voltage-dependent manner. Tolbutamide, a blocker of ATP-sensitive K+ (KATP) channels, had no effect on the currents. The single channel underlying the whole-cell IR K+ currents displayed inward rectification and had a conductance of 31 pS in symmetrical KCl-rich solutions. We demonstate that mRNA coding for IRK1 is expressed in this cell preparation. Possible functions for this channel are discussed.