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Ca2+- and voltage-activated K+ channels are found in many electrically excitable cells and have an important role in regulating electrical activity. 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 transport. Using patch-clamp methods 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.

Depolarization of pancreatic cells by exposure to high potassium solutions is associated with release of amylase. In the guinea pig, but not the mouse or cat, this Ca-dependent amylase secretion is resistant to atropine blockade, thus Scheele and Haymovits concluded that the enzyme secretion evoked by K depolarization does not involve release of transmitter from intrapancreatic nerves but is a consequence of Ca uptake into acinar cells mediated by the membrane depolarization. This hypothesis is inconsistent with current concepts of stimulus--secretion coupling in electrically non-excitable cells. The observation of Scheele and Haymovits could, however, also be explained by the release of a non-cholinergic, secretomotor transmitter as a consequence of the depolarization of intrapancreatic nerves. By adapting the technique of electrical field stimulation of isolated pancreatic segments to our studies of amylase secretion, we have now been able to demonstrate both cholinergic and non-cholinergic, non-adrenergic secretomotor nerves in the guinea pig pancreas. Excitation of the non-cholinergic nerves stimulates amylase secretion by a different intracellular coupling mechanism from that activated by cholinergic nerves or by peptides belonging to the cholecystokinin, gastrin or bombesin families.