A large variety of responses has been uncovered by recent investigations of conductance changes elicited by muscarinic agonists. In exocrine glands, the permeability to K+, Cl and Na+ ions is increased, and internal Ca2+ serves as a second messenger. Patch-clamp analysis of the secreting cells has revealed three types of Ca2+-dependent channels, which are respectively selective for K+, for Cl, and for monovalent cations. The channels differ in their sensitivity to the internal Ca2+ concentration, Ca,. K+-selective channels are partially activated at rest, with Ca, approx. 10 nmol I−1; Cl-selective channels are activated between 100 nmol l−1 and 1 μmoll−1; activation of cationic channels requires micromolar Ca, levels.

Cell-attached recordings, performed either on isolated cells or on cell clusters, show an activation of all three channel types upon application of acetylcholine. In whole-cell recordings, mostly K+-and Cl-selective channels are activated. The cell currents display slow oscillations linked to variations of Ca,. Whole-cell currents rise after a delay of approx. 1 s, and decay with a time constant of approx. 0·7 s upon removal of acetylcholine. They do not depend on extracellular Ca2+.

The recent demonstration that Ca2+-dependent currents can also be obtained when dialysing the cells with inositoltrisphosphate or with GTPγS, a non-hydrolysable analogue of guanosine triphosphate, opens promising leads to an analysis of intracellular events regulated by acetylcholine.

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