Whole-cell K+ current activation in response to voltages and carbachol in gastric parietal cells isolated from guinea pig

Abstract

Patch-clamp studies of whole-cell ionic currents were carried out in parietal cells obtained by collagenase digestion of the gastric fundus of the guinea pig stomach. Applications of positive command pulses induced outward currents. The conductance became progressively augmented with increasing command voltages, exhibiting an outwardly rectifying current-voltage relation. The current displayed a slow time course for activation. In contrast, inward currents were activated upon hyperpolarizing voltage applications at more negative potentials than the equilibrium potential to K+ (EK). The inward currents showed time-dependent inactivation and an inwardly rectifying current-voltage relation. Tail currents elicited by voltage steps which had activated either outward or inward currents reversed at near EK, indicating that both time-dependent and voltage-gated currents were due to K+ conductances. Both outward and inward K+ currents were suppressed by extracellular application of Ba2+, but little affected by quinine. Tetraethylammonium inhibited the outward current without impairing the inward current, whereas Cs+ blocked the inward current but not the outward current. The conductance of inward K+ currents, but not outward K+ currents, became larger with increasing extracellular K+ concentration. A Ca(2+)-mobilizing acid secretagogue, carbachol, and a Ca2+ ionophore, ionomycin, brought about activation of another type of outward K+ currents and voltage-independent cation currents. Both currents were abolished by cytosolic Ca2+ chelation. Quinine preferentially inhibited this K+ current. It is concluded that resting parietal cells of the guinea pig have two distinct types of voltage-dependent K+ channels, inward rectifier and outward rectifier, and that the cells have Ca(2+)-activated K+ channels which might be involved in acid secretion under stimulation by Ca(2+)-mobilizing secretagogues.