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On the mechanism of muscarinic inhibition of the cardiac Ca current

  • Excitable Tissues and Central Nervous Physiology
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Abstract

The mechanism of muscarinic inhibition of the Ca-current (I Ca) was studied in ventricular myocytes of guinea pig hearts and the following results were obtained. 1. Acetylcholine (ACh) in concentrations up to 10−4 M had little effect, if any, onI Ca in control cells. 2. ACh reduced the isoprenaline (ISP)-induced increase ofI Ca. The doseresponse-relation (ISP concentration vs.I Ca density) was shifted by ACh towards higher ISP concentrations. But both, at low and high ISP concentrations ACh had nor or little effect. 3. ACh was ineffective whenI Ca was increased by dialysing the cell with catalytic subunit of cAMP-dependent protein kinase or cAMP. 4. ACh reducedI Ca enhanced by isobutylmethylxanthine or by forskolin. 5. ACh did not depressI Ca when the cell was dialysed with the nonhydrolysable GTP-derivative, GMP-PNP. In this condition the β-adrenergic enhancement ofI Ca was also absent. 6. Pertussis toxin, which is known to inhibit the inhibitory transducerprotein (Ni), abolished the ACh response.

We concluded from these results that ACh depressesI Ca by inhibiting, via Ni, the cAMP production.

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Author notes

  1. M. Kameyama

    Present address: National Institute for Physiological Sciences, Myodaiji, 444, Okazaki, Japan

Authors and Affiliations

  1. II. Physiologisches Institut, Universität des Saarlandes, D-6650, Homburg/Saar, Federal Republic of Germany

    J. Hescheler, M. Kameyama & W. Trautwein

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  1. J. Hescheler
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  2. M. Kameyama
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  3. W. Trautwein
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This work was supported by the Deutsche Forschungsgemeinschaft, SFB 38 (Membranforschung), Project G

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Hescheler, J., Kameyama, M. & Trautwein, W. On the mechanism of muscarinic inhibition of the cardiac Ca current. Pflugers Arch. 407, 182–189 (1986). https://doi.org/10.1007/BF00580674

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