Abstract
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 obs...Continue Reading
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