Cardiac excitation-contraction coupling in the absence of Na+-Ca2+ exchange

被引:41
作者
Reuter, H
Henderson, SA
Han, TY
Mottino, GA
Frank, JS
Ross, RS
Goldhaber, JI
Philipson, KD [1 ]
机构
[1] Univ Calif Los Angeles, David Geffen Sch Med, Dept Physiol, Los Angeles, CA 90095 USA
[2] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA
[3] Univ Calif Los Angeles, David Geffen Sch Med, Cardiovasc Res Lab MRL 3 645, Los Angeles, CA 90095 USA
关键词
excitation-contraction coupling; Na+-Ca2+ exchanger;
D O I
10.1016/S0143-4160(03)00018-6
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
We investigate cardiac excitation-contraction coupling in the absence of sarcolemmal Na+-Ca2+ exchange using NCX1 knockout mice. Knock out of NCX1 is embryonic lethal, and we measure Ca2+ transients and contractions in heart tubes from embryos at day 9.5 post coitum. Immunoblot and electron microscopy both indicate that sarcoplasmic reticular membranes are diminished in the knock out (NCX-/-) heart tubes. Both Ni2+ and nifedipine block excitation-contraction coupling in NCX-containing (NCX+) and NCX-/- heart tubes indicating an essential role for the L-type Ca2+ current. Under basal conditions (1 Hz stimulation), the NCX-/- heart tubes have normal Ca2+ transients but are unable to maintain homeostasis when Ca2+ fluxes are increased by various interventions (increased stimulation frequency, caffeine, isoproterenol). In each case, the NCX-/- heart tubes respond to the intervention in a more deleterious manner (increased diastolic Ca2+, decreased Ca2+ transient) than the NCX+ heart tubes. Expression of the sarcolemmal Ca2+ pump was not upregulated. The sarcolemmal Ca2+ pump, however, was able to compensate surprisingly well for the absence of Na+-Ca2+ exchange under basal conditions. (C) 2003 Elsevier Science Ltd. All rights reserved.
引用
收藏
页码:19 / 26
页数:8
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