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Reduction of resting K+ current by metabotropic glutamate and muscarinic receptors in rat CA3 cells: mediation by G‐proteins.
Author(s) -
Guérineau N C,
Gähwiler B H,
Gerber U
Publication year - 1994
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.1994.sp019999
Subject(s) - metabotropic glutamate receptor , muscarinic acetylcholine receptor , acpd , chemistry , biophysics , patch clamp , metabotropic receptor , methoctramine , reversal potential , membrane potential , endocrinology , glutamate receptor , neuroscience , medicine , biology , receptor , muscarinic acetylcholine receptor m1 , biochemistry
1. Effects of 1S,3R‐1‐aminocyclopentane‐1,3‐dicarboxylate (1S,3R‐ACPD) acting at metabotropic glutamate receptors (mGluRs), and methacholine (MCh), acting at cholinergic muscarinic receptors, were investigated in CA3 neurones in hippocampal slice cultures using the patch‐clamp technique. 2. Both 1S,3R‐ACPD (10 microM) and MCh (0.5 microM) activated an inward current associated with a decrease in membrane conductance. The current was observed when the slow calcium‐dependent after‐hyperpolarizing current (IAHP) and the voltage‐dependent current (IM) were not activated, reversed close to the reversal potential for K+ (EK) (Erev = ‐92.8 +/‐ 10.7 and ‐89.2 +/‐ 8.6 mV for 1S,3R‐ACPD and MCh, respectively), varied linearly with membrane potential, and thus corresponds to a leak K+ current. 3. The decrease in K+ conductance elicited with 1S,3R‐ACPD (50 microM) was substantially reduced (> 70%) with bath application of (RS)‐alpha‐methyl‐4‐carboxyphenylglycine (MCPG, 1 mM), a selective mGluR antagonist and was not mimicked by the enantiomer 1R,3S‐ACPD (100 microM). 4. The effects of 1S,3R‐ACPD and MCh were mediated by activation of G‐proteins since no inward current could be elicited in GDP beta S‐loaded cells (500 microM). When cells were dialysed with GTP (100 microM) or GTP gamma S (250 microM), however, the amplitude of the current was significantly enhanced. 5. These findings provide evidence that G‐proteins couple the activation of mGluRs and muscarinic receptors to a decrease in leak K+ conductance.

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