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

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.