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Mechanism of muscarinic control of the high-threshold calcium current in rabbit sino-atrial node myocytes

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Abstract

The mechanism of the action of acetylcholine (ACh) on the L-type calcium current (I Ca,L) was examined using a whole-cell voltage-clamp technique in single sino-atrial myocytes from the rabbit heart. ACh depressed basal I Ca,L at concentrations in the range 0.05–10 μM, without previous β-adrenergic stimulation. The ACh-induced reduction of I Ca,L was reversed by addition of atropine, indicating that muscarinic receptors mediate it. Incubation of cells with a solution containing pertussis toxin led to abolition of the ACh effect, suggesting that this effect is mediated by G proteins activated by muscarinic receptors. Dialysis of cells with protein kinase inhibitor or 5′-adenylyl imidodiphosphate, inhibitors of the cAMP-dependent protein kinase, decreased basal I Ca,L by about 85% and suppressed the effect of ACh. The ACh effect was also absent in cells dialysed with a non-hydrolysable analogue of cAMP, 8-bromo-cAMP. The results suggest that, in basal conditions, a large part of the L-type calcium channels should be phosphorylated by protein kinase A stimulated by a high cAMP level correlated with a high adenylate cyclase activity. The depressing effect of ACh on I Ca,L may occur via inhibition of the high basal adenylate cyclase activity leading to a decrease of cAMP-dependent protein kinase stimulation and thus to a dephosphorylation of calcium channels.

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Authors and Affiliations

  1. Laboratoire de Physiologie Générale, CNRS U.R.A. 290, Faculté des Sciences, Université de Poitiers, F-86022, Poitiers Cedex, France

    J. Petit-Jacques, P. Bois, J. Bescond & J. Lenfant

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  1. J. Petit-Jacques
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  2. P. Bois
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  3. J. Bescond
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  4. J. Lenfant
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Petit-Jacques, J., Bois, P., Bescond, J. et al. Mechanism of muscarinic control of the high-threshold calcium current in rabbit sino-atrial node myocytes. Pflugers Arch. 423, 21–27 (1993). https://doi.org/10.1007/BF00374956

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  • DOI: https://doi.org/10.1007/BF00374956

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