Muscarinic suppression of the M-current is mediated by a rise in internal Ca²⁺ concentration

The role of intracellular Ca²⁺ in the muscarinic suppression of M-current was examined. Intracellular injection of Ca²⁺ buffer into cells in the intact ganglion reduced the response to muscarinic agonist. In similar experiments on isolated cells, Ca²⁺ buffer was introduced into the cytoplasm using a perfused recording pipette. Ca²⁺ buffer (20 mM) with the free Ca²⁺ concentration set to normal resting levels produced a reversible reduction of the muscarinic response. In a second line of investigation, it was found that pharmacological procedures designed to deplete internal stores of Ca²⁺ produced a decrease in the muscarinic response. These results, taken together with previous work, support the hypothesis that the muscarinic suppression of M-current is mediated by the release of Ca²⁺ from intracellular stores.