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PMID: 2428006 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

On the mechanism of muscarinic inhibition of the cardiac Ca current.

Pflugers Archiv : European journal of physiology ·Vol. 407 ·No. 2 ·1986-08-00 ·Pages 182-9

Hescheler J, Kameyama M, Trautwein W

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. Acetylcholine (ACh) in concentrations up to 10(-4) M had little effect, if any, on ICa in control cells. ACh reduced the isoprenaline (ISP)-induced increase of ICa. The dose-response-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. ACh was ineffective when ICa was increased by dialysing the cell with catalytic subunit of cAMP-dependent protein kinase or cAMP. ACh reduced ICa enhanced by isobutylmethylxanthine or by forskolin. ACh did not depress ICa when the cell was dialysed with the non-hydrolysable GTP-derivative, GMP-PNP. In this condition the beta-adrenergic enhancement of ICa was also absent. Pertussis toxin, which is known to inhibit the inhibitory transducer protein (Ni), abolished the ACh response. We concluded from these results that ACh depresses ICa by inhibiting, via Ni, the cAMP production.

MeSH Terms
1-Methyl-3-isobutylxanthine/pharmacology Acetylcholine/physiology Action Potentials/drug effects Animals Calcium/metabolism Colforsin/pharmacology Cyclic AMP/pharmacology Female Guanylyl Imidodiphosphate/pharmacology Guinea Pigs Heart/physiology Ion Channels/physiology Isoproterenol/pharmacology Male Perfusion Pertussis Toxin Protein Kinases/metabolism Virulence Factors, Bordetella/pharmacology
Chemicals
Ion Channels Virulence Factors, Bordetella Colforsin Guanylyl Imidodiphosphate Cyclic AMP Pertussis Toxin Protein Kinases Isoproterenol Acetylcholine Calcium 1-Methyl-3-isobutylxanthine
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Hescheler J
Kameyama M
Trautwein W
References (46)
46 references, click to expand
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Article Info
Journal
Pflugers Archiv : European journal of physiology
Abbr.
Pflugers Arch
ISSN
0031-6768
DOI
10.1007/BF00580674
Published
1986-08-00
Pages
182-9
Language
English
Region
Germany
NLM ID
0154720
Subset
IM
External Links
PubMed source DOI: 10.1007/BF00580674 View journal details
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