Adrenergic Stimulation Regulates Na+/Ca2+Exchanger Expression in Rat Cardiac Myocytes

K. L. Golden, Q. I. Fan, B. Chen, J. Ren, J. O»Connor and J. D. Marsh. Adrenergic Stimulation Regulates Na+/Ca2+Exchanger Expression in Rat Cardiac Myocytes. Journal of Molecular and Cellular Cardiology (2000) 32, 611–620. The Na/Ca exchanger protein encoded by the NCX1 gene provides the predominant mechanism for calcium efflux during cardiac relaxation. Because β -adrenergic stimulation increases expression of Ca2+channels (Ca2+influx) in cardiac myocytes, we tested the hypothesis that isoproterenol would concomitantly augment expression of NCX1. Four hour treatment of neonatal myocytes with isoproterenol significantly increased NCX1 gene and protein expression, and increased the rate of transcript initiation. Alpha-adrenergic stimulation significantly decreases NCX1 mRNA levels. Calcium transient measurements revealed that for cells that had been pretreated with isoproterenol there was a faster relaxation rate of the Ca2+transient in the presence of thapsigargin, indicating an enhanced rate of intracellular Ca2+removal. We conclude that effectors that increase calcium channel expression in neonatal myocytes also augments NCX1 gene and protein expression over a similar time course, and that this is due to enhanced NCX1 transcription. The regulation of expression of NCX1 by adrenergic pathways may play an important role in regulation of excitation–contraction coupling in cardiac myocytes.