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 (Iahp), the M-current (Im), and a leak K+ conductance (Ileak). Based on pharmacological evidence and the abundant localization of M1 receptors in pyramidal cells, it has been assumed that the M1 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 M1 knockout mice revealed no significant difference in the degree of inhibition of Iahp, Im, or Ileak by the mAChR agonist, carbachol (CCh), as compared with wildtype controls. In addition, the M1-toxin was not able to block CCh's inhibition of the Iahp, Im, or Ileak These data demonstrate that the M1 receptor is not involved in increasing CA1 pyramidal cell excitability by mediating ACh effects on these K+ conductances.
Rouse
S T
ST
Department of Pharmacology, Emory University School of Medicine, Atlanta, GA 30322, USA.
Hamilton
S E
SE
Potter
L T
LT
Nathanson
N M
NM
Conn
P J
PJ
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D004546:Elapid Venoms / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology* / Q000187:drug effects; D015640:Ion Channel Gating / Q000187:drug effects*; D017136:Ion Transport / Q000187:drug effects*; D051379:Mice; D018345:Mice, Knockout; D018721:Muscarinic Agonists / Q000494:pharmacology; D018727:Muscarinic Antagonists / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D010890:Pirenzepine / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism*; D015221:Potassium Channels / Q000187:drug effects*; D017966:Pyramidal Cells / Q000187:drug effects*; D043643:Receptor, Muscarinic M1; D011976:Receptors, Muscarinic / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
D004546:Elapid Venoms; D018721:Muscarinic Agonists; D018727:Muscarinic Antagonists; D015221:Potassium Channels; D043643:Receptor, Muscarinic M1; D011976:Receptors, Muscarinic; C083667:m1-toxin; D010890:Pirenzepine; D001285:Atropine; D002217:Carbachol; D011188:Potassium