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Muscarinic suppression of the M‐current in the rat sympathetic ganglion is mediated by receptors of the M 1 ‐subtype
Author(s) -
Marrion N.V.,
Smart T.G.,
Marsh S.J.,
Brown D.A.
Publication year - 1989
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1989.tb12630.x
Subject(s) - muscarine , oxotremorine , muscarinic acetylcholine receptor , pirenzepine , chemistry , sympathetic ganglion , endocrinology , medicine , tetraethylammonium , biophysics , depolarization , carbachol , reversal potential , muscarinic acetylcholine receptor m2 , muscarinic acetylcholine receptor m3 , superior cervical ganglion , patch clamp , receptor , biology , biochemistry , potassium , organic chemistry
1 Under voltage‐clamp dissociated adult and foetal rat superior cervical ganglion (s.c.g.) cells exhibited a non‐inactivating voltage‐ and time‐dependent component of K + current termed the M‐current (I M ). I M was detected and measured from the current decay during hyperpolarizing voltage steps applied from potentials where I M was pre‐activated. 2 Neither the resting membrane current nor the amplitude of these current decay relaxations were reduced by omitting Ca from the bathing fluid, showing that the M‐current was not a ‘Ca‐activated’ K‐current dependent on a primary Ca‐influx. Concentrations of (+)‐tubocurarine sufficient to block the slow Ca‐activated K‐current I AHP did not inhibit I M or antagonize the effect of muscarinic agonists on I M , showing that I M was not contaminated by I AHP . Tetraethylammonium (1 m m ), which blocks the fast Ca‐activated K‐current I c , produced a small inhibition of I M . This was not due to contamination of I M by I c since muscarinic agonists did not consistently block I c . 3 The muscarinic agonists muscarine, oxotremorine, McN‐A‐343 and methacholine reversibly suppressed I M , resulting in an inward (depolarizing) current. The rank order of potency was: oxotremorine ≥ muscarine > McN‐A‐343 > methacholine. 4 The suppression of I M by muscarine was similar in cultured cells derived from adult and foetal tissue to that seen in the intact ganglia. 5 I M ‐suppression by muscarine was inhibited by pirenzepine (Pz) and AF‐DX 116 with mean p K B values of 7.53 ± 0.13 ( n = 3) and 6.02 ± 0.13 ( n = 4) respectively. 6 The suppression of I M by muscarinic agonists was not affected by gallamine (10–30 μ m ). 4‐Diphenylacetoxy‐N‐methylpiperidine methiodide inhibited the response at 300 nM. 7 Pirenzepine inhibited the contractions of the guinea‐pig isolated ileum produced by muscarine with a mean p K B of 6.37 ± 0.03 ( n = 8). 8 These results suggest that the receptors mediating suppression of the M‐current accord with those designated pharmacologically as M 1 and that these receptors reach maturity at a very early stage in the development of the rat s.c.g.