Cardiac-specific overexpression of the alpha(1) subunit of the L-type voltage-dependent Ca(2+) channel in transgenic mice. Loss of isoproterenol-induced contraction

James N Muth; Hiroshi Yamaguchi; Gabor Mikala; Ingrid L Grupp; William Lewis; Heping Cheng; Long-Sheng Song; Edward G Lakatta; Gyula Varadi; Arnold Schwartz

doi:10.1074/jbc.274.31.21503

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Cardiac-specific overexpression of the alpha(1) subunit of the L-type voltage-dependent Ca(2+) channel in transgenic mice. Loss of isoproterenol-induced contraction

Journal article

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Peer reviewed

Cardiac-specific overexpression of the alpha(1) subunit of the L-type voltage-dependent Ca(2+) channel in transgenic mice. Loss of isoproterenol-induced contraction

James N Muth, Hiroshi Yamaguchi, Gabor Mikala, Ingrid L Grupp, William Lewis, Heping Cheng, Long-Sheng Song, Edward G Lakatta, Gyula Varadi and Arnold Schwartz

The Journal of biological chemistry, Vol.274(31), pp.21503-21506

07/30/1999

DOI: 10.1074/jbc.274.31.21503

PMID: 10419451

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Abstract

The L-type voltage-dependent calcium channel (L-VDCC) regulates calcium influx in cardiac myocytes. Activation of the beta-adrenergic receptor (betaAR) pathway causes phosphorylation of the L-VDCC and that in turn increases Ca(2+) influx. Targeted expression of the L-VDCC alpha(1) subunit in transgenic (Tg) mouse ventricles resulted in marked blunting of the betaAR pathway. Inotropic and lusitropic responses to isoproterenol and forskolin in Tg hearts were significantly reduced. Likewise, Ca(2+) current augmentation induced by iso- proterenol and forskolin was markedly depressed in Tg cardiomyocytes. Despite no change in betaAR number, isoproterenol-stimulated adenylyl cyclase activity was absent in Tg membranes and NaF and forskolin responses were reduced. We postulate an important pathway for regulation of the betaAR by Ca(2+) channels.

Echocardiography

Calcium - metabolism

Colforsin - pharmacology

Heart - physiology

Humans

Myocardial Contraction - physiology

Ventricular Function, Left - drug effects

Myocardial Contraction - drug effects

Male

Mice, Transgenic

Adenylyl Cyclases - metabolism

Receptors, Adrenergic, beta - physiology

Macromolecular Substances

Heart Ventricles

Animals

Calcium Channels, N-Type

Isoproterenol - pharmacology

Myocardium - metabolism

Heart - drug effects

Female

Ventricular Function, Left - physiology

Mice

Receptors, Adrenergic, beta - drug effects

Calcium Channels - genetics

Details

Title: Subtitle: Cardiac-specific overexpression of the alpha(1) subunit of the L-type voltage-dependent Ca(2+) channel in transgenic mice. Loss of isoproterenol-induced contraction
Creators: James N Muth - Institute of Molecular Pharmacology and Biophysics, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267, USA
Hiroshi Yamaguchi
Gabor Mikala
Ingrid L Grupp
William Lewis
Heping Cheng
Long-Sheng Song
Edward G Lakatta
Gyula Varadi
Arnold Schwartz
Resource Type: Journal article
Publication Details: The Journal of biological chemistry, Vol.274(31), pp.21503-21506
DOI: 10.1074/jbc.274.31.21503
PMID: 10419451
NLM abbreviation: J Biol Chem
ISSN: 0021-9258
eISSN: 1083-351X
Grant note: R01 R37HL43231 / NHLBI NIH HHS T32 HL 07382 / NHLBI NIH HHS P01 HL22619 / NHLBI NIH HHS
Language: English
Date published: 07/30/1999
Academic Unit: Cardiovascular Medicine; Fraternal Order of Eagles Diabetes Research Center; Biochemistry and Molecular Biology; Internal Medicine
Record Identifier: 9984094635302771

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