Existence of muscarinic suppression of a K current in PC-12 pheochromocytoma cells

Muscarinic influence on membrane currents of PC-12 pheochromocytoma cells were investigated with whole cell voltage-clamp methods. An outward K current was observed when depolarizing voltage steps were applied to the cells. Methacholine (MCh, 300 μM), a selective agonist for muscarinic receptors, partially suppressed the K current, and the suppression was enhanced by removal of external Ca. The effect of MCh was antagonized by a low dose (100 nM) of atropine. Nicotine (10 μM) induced an inward current in these cells but did not affect the K current activated by depolarizing voltage steps. A Ba current flowing through voltage-gated Ca channels was not changed by MCh. The results indicate the existence of a MCh-sensitive K current in PC-12 cells and suggest that the membrane currents of these cells are modulated by cholinergic agents through muscarinic mechanisms in addition to well-known nicotinic mechanisms.