Muscarinic-induced modulation of potassium conductances is unchanged in mouse hippocampal pyramidal cells that lack functional M-1 receptors

Activation of muscarinic acetylcholine (ACh) receptors (mAChRs) increases e xcitability of pyramidal cells by inhibiting several K+ conductances, inclu ding the after-hyperpolarization current (I-ahp), the M-current (I-m), and a leak K+ conductance (I-leak) Based on pharmacological evidence and the ab undant localization of M-1 receptors in pyramidal cells, it has been assume d that the M-1 receptor is responsible for mediating these effects. However , given the poor selectivity of the pharmacological agents used to characte rize these mAChR responses, rigorous characterization of the receptor subty pes that mediate these actions has not been possible. Surprisingly, patch c lamp recording from CA1 pyramidal cells in M-1 knockout mice revealed no si gnificant 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 i nvolved in increasing CA1 pyramidal cell excitability by mediating ACh effe cts on these K+ conductances. (C) 2000 Elsevier Science Ireland Ltd. All ri ghts reserved.