Muscarinic-induced modulation of potassium conductances is unchanged in mouse hippocampal pyramidal cells that lack functional M1 receptors

Activation of muscarinic acetylcholine (ACh) receptors (mAChRs) increases excitability of pyramidal cells by inhibiting several K+ conductances, including the after-hyperpolarization current (I-ahp), the M-current (I-m), and a leak K+ conductance (I-leak) Based on pharmacological evidence and the abundant localization of M-1 receptors in pyramidal cells, it has been assumed that the M-1 receptor is responsible for mediating these effects. However, given the poor selectivity of the pharmacological agents used to characterize these mAChR responses, rigorous characterization of the receptor subtypes that mediate these actions has not been possible. Surprisingly, patch clamp recording from CA1 pyramidal cells in M-1 knockout mice revealed no significant difference in the degree of inhibition of I-ahp,I- I-m, or I-leak by the mAChR agonist, carbachol (CCh), as compared with wildtype controls. In addition, the M-1-toxin was not able to block CCh's inhibition of the I-ahp, I-m, or I-leak. These data demonstrate that the M-1 receptor is not involved in increasing CA1 pyramidal cell excitability by mediating ACh effects on these K+ conductances. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.