| 10899051 |
Mitarai S, Reed TD, Yatani A: Changes in ionic currents and beta-adrenergic receptor signaling in hypertrophied myocytes overexpressing G alpha (q). Am J Physiol Heart Circ Physiol. 2000 Jul;279(1):H139-48.
Transgenic overexpression of G alpha (q) causes cardiac hypertrophy and depressed contractile responses to beta-adrenergic receptor agonists. The electrophysiological basis of the altered myocardial function was examined in left ventricular myocytes isolated from transgenic (G alpha (q)) mice. Action potential duration was significantly prolonged in G alpha (q) compared with nontransgenic (NTG) myocytes. The densities of inward rectifier K (+) currents, transient outward K (+) currents (I (to)), and Na (+)/Ca (2+) exchange currents were reduced in G alpha (q) myocytes. Consistent with functional measurements, Na (+)/Ca (2+) exchanger gene expression was reduced in G alpha (q) hearts. Kinetics or sensitivity of I (to) to 4-aminopyridine was unchanged, but 4-aminopyridine prolonged the action potential more in G alpha (q) myocytes. Isoproterenol increased L-type Ca (2+) currents (I (Ca)) in both groups, with a similar EC (50), but the maximal response in G alpha (q) myocytes was approximately 24% of that in NTG myocytes. In NTG myocytes, the maximal increase of I (Ca) with isoproterenol or forskolin was similar. In G alpha (q) myocytes, forskolin was more effective and enhanced I (Ca) up to approximately 55% of that in NTG myocytes. These results indicate that the changes in ionic currents and multiple defects in the beta-adrenergic receptor/Ca (2+) channel signaling pathway contribute to altered ventricular function in this model of cardiac hypertrophy. |
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