Circulation Journal
Online ISSN : 1347-4820
Print ISSN : 1346-9843
ISSN-L : 1346-9843
Experimental Investigation
Beta-, Not Alpha-Adrenergic Stimulation Enhances Conduction Velocity in Cultures of Neonatal Cardiomyocytes
Teun P. de BoerHarold V.M. van RijenMarcel A.G. Van der HeydenBart KokTobias OpthofMarc A. VosHabo J. JongsmaJacques M.T. de BakkerToon A.B. van Veen
Author information
JOURNAL FREE ACCESS

2007 Volume 71 Issue 6 Pages 973-981

Details
Abstract

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=24 h. Under control conditions (n=7), CV at t=0 (30.9±1.9 cm/s) and t=24 (32.4±4.4 cm/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 ±2.0 cm/s at t=0 to 34.8±2.2 cm/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 α1c (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 α-adrenergic agonist phenylephrine did neither affect CV nor the expression of the connexin isoforms, SCN5A and α1c. 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 α1c and SCN5A in β-adrenergic stimulated cells, which may explain the observed increase in CV. (Circ J 2007; 71: 973 - 981)

Content from these authors
© 2007 THE JAPANESE CIRCULATION SOCIETY
Previous article Next article
feedback
Top