Chronic α-adrenergic receptor stimulation modulates the contractile phenotype of cardiac myocytes in vitro

被引:1
|
作者
Satoh, N
Suter, TM
Liao, R
Colucci, WS
机构
[1] Boston Univ, Med Ctr, Cardiovasc Sect, Boston, MA 02118 USA
[2] Boston Univ, Sch Med, Myocardial Biol Unit, Boston, MA 02118 USA
[3] Boston Univ, Sch Med, Cardiac Muscle Res Lab, Boston, MA 02118 USA
关键词
myocytes; calcium; sarcoplasmic reticulum; ion channels; receptors; adrenergic; alpha;
D O I
暂无
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background-Heart failure is characterized by contractile dysfunction of the myocardium and elevated sympathetic activity. We tested the hypothesis that chronic alpha -adrenergic (alpha -ADR) stimulation modifies the molecular and contractile phenotype of cardiac myocytes. Methods and Results-Adult rat ventricular myocytes in culture were exposed to alpha -ADR stimulation (norepinephrine + propranolol) for 48 hours. alpha -ADR stimulation decreased the mRNAs for sarcoplasmic reticulum Ca2+-ATPase and Ca2+ release channel by 56% and 52%, respectively, and increased mRNA and protein for the Na+-Ca2+ exchanger by 70% and 39%, respectively. After washout of the alpha -ADR agonist, simultaneous measurement of [Ca2+](i) transients with fura 2 and myocyte shortening by video edge-detection showed that [Ca2+](i) amplitude and myocyte shortening were decreased in alpha -ADR-treated myocytes, and the time to peak and time from peak to 80% decline of both [Ca2+](i) and myocyte shortening were increased. The concentration-response curve for myocyte shortening by the Na+ channel activator veratridine was shifted leftward in alpha -ADR-stimulated myocytes (EC50, 21.6+/-4.6 versus 105.8+/-10.5 nmol/L, P<0.001). Conclusions-Chronic <alpha>-ADR stimulation of cardiac myocytes causes decreases in the expression of sarcoplasmic reticulum Ca2+-ATPase and the Ca2+ release channel that are associated with decreases in [Ca2+](i) and contractility. alpha -ADR stimulation simultaneously increases Na+-Ca2+ exchanger expression, thereby increasing sensitivity to intracellular Na+.
引用
收藏
页码:2249 / 2254
页数:6
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