Quantification of Ca²⁺-activated K⁺ channels under hormonal control in pig pancreas acinar cells

Abstract

Ca²⁺- and voltage-activated K⁺ channels are found in many electrically excitable cells and have an important role in regulating electrical activity^1–4. Recently, the large K⁺ channel has been found in the baso-lateral plasma membranes of salivary gland acinar cells, where it may be important in the regulation of salt transport⁵. Using patch-clamp methods^6,7 to record single-channel currents from excised fragments of baso-lateral acinar cell membranes in combination with current recordings from isolated single acinar cells and two- and three-cell clusters, we have now for the first time characterized the K⁺ channels quantitatively. In pig pancreatic acini there are 25–60 K⁺ channels per cell with a maximal single channel conductance of about 200 pS. We have quantified the relationship between internal ionized Ca²⁺ concentration ([Ca²⁺]_i) membrane potential and open-state probability (p) of the K⁺ channel. By comparing curves obtained from excised patches relating membrane potential to p, at different levels of [Ca²⁺]_i, with similar curves obtained from intact cells, [Ca²⁺]_i in resting acinar cells was found to be between 10⁻⁸ and 10⁻⁷ M. In microelectrode experiments acetylcholine (ACh), gastrin–cholecystokinin (CCK) as well as bombesin peptides evoked Ca²⁺-dependent opening of the K⁺ conductance pathway, resulting in membrane hyperpolarization. The large K⁺ channel, which is under strict dual control by internal Ca²⁺ and voltage, may provide a crucial link between hormone-evoked increase in internal Ca²⁺ concentration and the resulting NaCl-rich fluid secretion^5,8.