AJP - Endocrinology and Metabolism, Vol 269, Issue 1 E43-E52, Copyright © 1995 by American Physiological Society

ARTICLES

Cation channel activated by muscarinic agonists on porcine adrenal chromaffin cells

E. J. Forsberg, Q. Li and Y. Xu
Department of Physiology, University of Wisconsin Medical School, Madison 53706, USA.

A large portion (70%) of the secretory response to muscarinic agonists in porcine adrenal chromaffin cells has previously been shown to be dependent on extracellular Ca2+ (Xu et al., J. Neurochem. 56: 1899-1896, 1991). Results presented here show that muscarinic agonists activate a cation-selective channel which is permeable to divalent cations. The muscarinic agonist, methacholine, was found to activate the uptake of Mn2+, which paralleled the ability of methacholine to activate 45Ca2+ uptake as shown previously. Secretion induced by methacholine was not affected by nifedipine, a compound that inhibits dihydropyridine-sensitive voltage-gated Ca2+ channels. In voltage-clamped cells, methacholine activated whole cell currents, which reversed at approximately -20 mV in standard salt solutions. However, with the standard whole cell configuration, the currents were slow to activate and were often erratic. In contrast, when the perforated-patch (nystatin) technique was used to measure whole cell currents, methacholine rapidly activated sustained inward currents. Ion-substitution experiments indicated that the inward currents were carried by Na+, Ba2+, or Ca2+ but not by Cl-. Single-channel currents activated by methacholine were observed in outside-out vesicles, which were electrically accessed using the perforated-patch technique. These channels reversed at -15 mV, had a slope conductance of 20 pS, and were 14-fold more likely to be open in the presence of methacholine. These channels are probably responsible for the extracellular Ca(2+)-dependent secretory response to muscarinic receptor stimulation in porcine adrenal chromaffin cells.

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