Adrenergic stimulation regulates Na(+)/Ca(2+)Exchanger expression in rat cardiac myocytes.
The Na/Ca exchanger protein encoded by the NCX1 gene provides the predominant mechanism for calcium efflux during cardiac relaxation. Because beta -adrenergic stimulation increases expression of Ca(2+)channels (Ca(2+)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 Ca(2+)transient in the presence of thapsigargin, indicating an enhanced rate of intracellular Ca(2+)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.
Golden
K L
KL
Program in Molecular and Cellular Cardiology, Wayne State University, Detroit, MI 48201, USA.
Fan
Q I
QI
Chen
B
B
Ren
J
J
O'Connor
J
J
Marsh
J D
JD
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000187:drug effects; D006352:Heart Ventricles / Q000166:cytology / Q000378:metabolism*; D007545:Isoproterenol / Q000494:pharmacology; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D010656:Phenylephrine / Q000494:pharmacology; D012333:RNA, Messenger; D051381:Rats; D017207:Rats, Sprague-Dawley; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D019831:Sodium-Calcium Exchanger / Q000235:genetics*; D014158:Transcription, Genetic / Q000187:drug effects
D000316:Adrenergic alpha-Agonists; D000318:Adrenergic beta-Agonists; D012333:RNA, Messenger; D011943:Receptors, Adrenergic, beta; D019831:Sodium-Calcium Exchanger; C110374:sodium-calcium exchanger 1; D010656:Phenylephrine; D007545:Isoproterenol; D002118:Calcium