Beta-, Not Alpha-Adrenergic Stimulation Enhances Conduction Velocity in Cultures of Neonatal Cardiomyocytes
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概要
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Background During both cardiac maturation and myopathy, elevated levels of circulating catecholamines coincide with alterations in impulse propagation. An in vitro model of cultured cardiomyocytes was used to study the effects of adrenergic stimulation on the conduction characteristics of immature heart cells. Methods and Results Neonatal rat cardiomyocytes were cultured on preparations designed to measure conduction velocity (CV). CV was measured on the same preparation twice at t=0 and at t=24h. Under control conditions (n=7), CV at t=0 (30.9±1.9cm/s) and t=24 (32.4±4.4cm/s) was similar (p=0.70). Immunohistochemistry revealed expression of the gap junction proteins connexin (Cx) 40, Cx43 and Cx45, with Cx43 being highly predominant. Stimulation for 24 h with the β-adrenergic agonist isoproterenol (ISO) significantly increased CV from 28.0±2.0cm/s at t=0 to 34.8±2.2cm/s at t=24 (p=0.002, n=5). Microelectrode recordings showed a faster upstroke of the action potential (AP) of ISO-treated cells. Reverse transcribed-polymerase chain reactions (RT-PCR) showed that ISO increased expression of SCN5A and αIc (α-subunit of the cardiac sodium and L-type calcium channel, respectively). Stimulation of cells with ISO did not induce alterations in distribution or expression of Cx40, Cx43 and Cx45 (both mRNA and protein), but slightly increased the phosphorylation of Cx43. Stimulation for 24 h with the a-adrenergic agonist phenylephrine did neither affect CV nor the expression of the connexin isoforms, SCN5A and αIc. Conclusions Alpha- and β-adrenergic stimulation differently affect propagation of the electric impulse, which is primarily not caused by a differential effect on intercellular coupling. RT-PCR analysis and an enhanced AP upstroke velocity indicate a higher functional expression level of αIc and SCN5A in β-adrenergic stimulated cells, which may explain the observed increase in CV.
- 社団法人日本循環器学会の論文
- 2007-05-20
著者
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Rijen Harold
Heart Lung Center Utrecht Department Of Medical Physiology
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Boer Teun
Heart Lung Center Utrecht, Department of Medical Physiology
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Heyden Marcel
Heart Lung Center Utrecht, Department of Medical Physiology
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Kok Bart
Heart Lung Center Utrecht, Department of Medical Physiology
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Optho Tobias
Heart Lung Center Utrecht, Department of Medical Physiology
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Vos Marc
Heart Lung Center Utrecht, Department of Medical Physiology
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Jongsma Habo
Heart Lung Center Utrecht, Department of Medical Physiology
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Bakker Jacques
Heart Lung Center Utrecht, Department of Medical Physiology
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Veen Toon
Heart Lung Center Utrecht, Department of Medical Physiology
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Boer Teun
Heart Lung Center Utrecht Department Of Medical Physiology
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Veen Toon
Heart Lung Center Utrecht Department Of Medical Physiology
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Bakker Jacques
Heart Lung Center Utrecht Department Of Medical Physiology:interuniversity Cardiology Institute Of T
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Vos Marc
Heart Lung Center Utrecht Department Of Medical Physiology
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Kok Bart
Heart Lung Center Utrecht Department Of Medical Physiology
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Optho Tobias
Heart Lung Center Utrecht Department Of Medical Physiology:experimental And Molecular Cardiology Aca
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Jongsma Habo
Heart Lung Center Utrecht Department Of Medical Physiology
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Heyden Marcel
Heart Lung Center Utrecht Department Of Medical Physiology