Muscarinic response in rat lacrimal glands

Abstract

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, Cai. K+-selective channels are partially activated at rest, with Cai approx. 10 nmol l-1; Cl(-)-selective channels are activated between 100 nmol l-1 and 1 mumol l-1; activation of cationic channels requires micromolar Cai 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 Cai. 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 GTP gamma S, a non-hydrolysable analogue of guanosine triphosphate, opens promising leads to an analysis of intracellular events regulated by acetylcholine.