Ca2+-activated outward-rectifier K+ channels and histamine release by rat gastric enterochromaffin-like cells

Gastric enterochromaffin-like (ECL) cells were isolated from rat gastric fundic mucosa by Percoll density-gradient centrifugation and counter-flow elutriation. About 67% of cells in the purified cell suspension were ECL cells, which were reacted with anti-histidine decarboxylase antibody. A23187, a calcium ionophore, at 0.1-10 μM induced histamine release from the ECL cell-rich suspension, indicating that the Ca²⁺ pathway is involved in the mechanism of histamine release from ECL cells. A23187 at 5 μM significantly increased outward-rectifier cationic current in 62% of cells in the ECL cell-rich fraction. A23187-sensitive cells showed acridine orange uptake. In single-channel recordings, a Ca²⁺-dependent outward-rectifier K⁺ channel of large conductance (146 ± 22 picosiemens) was found in the cell that showed acridine orange uptake. The channel opened in a voltage-dependent manner at 0.1 μM of intracellular free Ca²⁺ concentration. These results may suggest that opening of the Ca²⁺-activated K⁺ channel is one of the steps involved in the mechanism of histamine release in ECL cells.