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Pflügers Archiv

, Volume 407, Issue 2, pp 182–189 | Cite as

On the mechanism of muscarinic inhibition of the cardiac Ca current

  • J. Hescheler
  • M. Kameyama
  • W. Trautwein
Excitable Tissues and Central Nervous Physiology

Abstract

The mechanism of muscarinic inhibition of the Ca-current (ICa) 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, onICa in control cells. 2. ACh reduced the isoprenaline (ISP)-induced increase ofICa. The doseresponse-relation (ISP concentration vs.ICa 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 whenICa was increased by dialysing the cell with catalytic subunit of cAMP-dependent protein kinase or cAMP. 4. ACh reducedICa enhanced by isobutylmethylxanthine or by forskolin. 5. ACh did not depressICa when the cell was dialysed with the nonhydrolysable GTP-derivative, GMP-PNP. In this condition the β-adrenergic enhancement ofICa 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 depressesICa by inhibiting, via Ni, the cAMP production.

Key words

Cardiac myocytes Ca current Muscarinic inhibition Adenylate cyclase 

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Copyright information

© Springer-Verlag 1986

Authors and Affiliations

  • J. Hescheler
    • 1
  • M. Kameyama
    • 1
  • W. Trautwein
    • 1
  1. 1.II. Physiologisches InstitutUniversität des SaarlandesHomburg/SaarFederal Republic of Germany

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