Cardiac excitation-contraction coupling in the absence of Na+-Ca2+ exchange
Cardiac excitation-contraction coupling in the absence of Na+-Ca2+ exchange
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DOI：
10.1016/s0143-4160(03)00018-6
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发表时间：
2003-07-01
期刊：
影响因子：
4
通讯作者：
Philipson, KD
中科院分区：
文献类型：
--
作者：
Reuter, H;Henderson, SA;Philipson, KD
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.
