INWARDLY RECTIFYING K-II CELLS ISOLATED FROM FETAL GUINEA-PIG LUNG - REGULATION BY G-PROTEIN-DEPENDENT AND MG2+-DEPENDENT PATHWAYS( CURRENTS OF ALVEOLAR TYPE)

K+ currents in alveolar type II tells, isolated from fetal guinea-pig lung, were studied using the whole-cell patch-clamp technique. Inwardl y 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 poten tial moved from 0 mV to -69 mV, indicating high KC selectivity. In rec ordings with an intracellular KCl-rich solution, containing 1.12 mM Mg 2+ and 10(-8) M free Ca2+, IR K+ currents slowly diminished with time. Addition of the irreversible G protein activator, guanosine 5'-O-(3-t hiotriphosphate) (GTP [gamma-S]), to the intracellular solution accele rated the rate of current run-down. In experiments where the intracell ular solution was Mg2+ free, current run-down was abolished. The rate of current run-down was found to increase with increasing free intrace llular [Mg2+] Raising the intracellular free [Ca2+] to 10(-6) M under Mg2+-free conditions had no effect on the K+ currents. Extracellular B a2+ blocked the IR K+ currents in a concentration- and voltage-depende nt manner. Tolbutamide, a blocker of ATP-sensitive K+ (K-ATP) channels , had no effect on the currents. The single channel underlying the who le-cell IR K+ currents displayed inward rectification and had a conduc tance of 31 pS in symmetrical KCl-rich solutions. We demonstate that m RNA coding for IRK1 is expressed in this cell preparation. Possible fu nctions for this channel are discussed.