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In vivo downregulation of M 2 receptors revealed by measurement of muscarinic K + current in cultured guinea‐pig atrial myocytes
Author(s) -
Bünemann Moritz,
Brandts Bodo,
Pott Lutz
Publication year - 1997
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 - 10.1111/j.1469-7793.1997.549bm.x
Subject(s) - carbachol , muscarinic acetylcholine receptor , downregulation and upregulation , acetylcholine , endocrinology , medicine , myocyte , receptor , guinea pig , acetylcholine receptor , chemistry , muscarinic acetylcholine receptor m3 , patch clamp , in vivo , in vitro , biology , biochemistry , gene , microbiology and biotechnology
1 Muscarinic K + current ( I K(ACh) ) elicited by acetylcholine (ACh) was measured in guinea‐pig atrial myocytes, which were either freshly isolated or cultured for up to 8 days. 2 The half‐time of activation of inward I K(ACh) by a saturating concentration (10 μ m ) of ACh decreased from ∼400 ms (in freshly isolated cells) to 250 ms after 6 days in culture. This was paralleled by an increase in the fast desensitizing component of I K(ACh) . The density of steady‐state currents was not changed. Downregulation of M 2 receptors by long‐term treatment of isolated myocytes with carbachol in vitro had opposite effects. 3 The EC 50 of ACh for the activation of steady‐state − K( ACh) was reduced from 5 × 10 7 M (day 0) to 8 × 10 8 m (day 6). The shift in EC 50 occurred with a half‐time of about 2 days, similar to the recovery from downregulation induced by treating atrial myocytes with carbachol in vitro.4 The increase in sensitivity to ACh can be accounted for by an ∼6‐fold increase in the density of M 2 receptors. 5 It is concluded that sensitization in culture reflects recovery from downregulation of M 2 receptors due to the tonic vagal input to the heart in the intact animal.