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The role of Ca 2+ stores in the muscarinic inhibition of the K + current I K(SO) in neonatal rat cerebellar granule cells
Author(s) -
Boyd David F.,
Millar Julie A.,
Watkins Christopher S.,
Mathie Alistair
Publication year - 2000
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.1469-7793.2000.00321.x
Subject(s) - muscarine , thapsigargin , muscarinic acetylcholine receptor , methoctramine , chemistry , depolarization , phospholipase c , biophysics , acetylcholine , oxotremorine , muscarinic agonist , medicine , carbachol , ionomycin , endocrinology , muscarinic acetylcholine receptor m3 , microbiology and biotechnology , endoplasmic reticulum , biology , receptor , intracellular , biochemistry
1 Cerebellar granule neurons (CGNs) possess a standing outward potassium current ( I K(SO) ) which shares many similarities with current through the two‐pore domain potassium channel TASK‐1 and which is inhibited following activation of muscarinic acetylcholine receptors. 2 The action of muscarine on I K(SO) was unaffected by the M 2 receptor antagonist methoctramine (100 n M ) but was blocked by the M 3 antagonist zamifenacin, which, at a concentration of 100 n M , shifted the muscarine concentration‐response curve to the right by around 50‐fold. 3 Surprisingly, M 3 receptor activation rarely produced a detectable increase in [Ca 2+ ] i unless preceded by depolarization of the cells with 25 m M K + . Experiments with thapsigargin and ionomycin suggested that the endoplasmic reticulum Ca 2+ stores in CGNs were depleted at rest. In contrast, cerebellar glial cells in the same fields of cells possessed substantial endoplasmic reticulum Ca 2+ stores at rest. 4 Pretreatment of the cells with BAPTA AM, thapsigargin or the phospholipase C (PLC) inhibitor U‐73122 all blocked the muscarine‐induced Ca 2+ signal but had little or no effect on muscarinic inhibition of I K(SO) . Raising [Ca 2+ ] i directly with ionomycin caused a small but significant inhibition of I K(SO) . 5 It is concluded that muscarine acts on M 3 muscarinic acetylcholine receptors both to inhibit I K(SO) and to mobilize Ca 2+ from intracellular stores in CGNs. While the mobilization of Ca 2+ occurs through activation of PLC, this does not seem to be the primary mechanism underlying muscarinic inhibition of I K(SO) .