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

• Published in: Cell calcium (Edinburgh) Vol. 34; no. 1; pp. 19 - 26
• Main Authors: Reuter, Hannes, Henderson, Scott A, Han, Tieyan, Mottino, Giuliano A, Frank, Joy S, Ross, Robert S, Goldhaber, Joshua I, Philipson, Kenneth D
• Format: Journal Article
• Language: English
• Published: Netherlands 01.07.2003
• Subjects: Action Potentials - drug effects; Action Potentials - physiology; Animals; Caffeine - pharmacology; Calcium - metabolism; Calcium Channel Blockers - pharmacology; Calcium Channels, L-Type - drug effects; Calcium Channels, L-Type - metabolism; Calcium Signaling - drug effects; Calcium Signaling - physiology; Calcium-Transporting ATPases - metabolism; Fetus; Intracellular Membranes - drug effects; Intracellular Membranes - metabolism; Intracellular Membranes - ultrastructure; Isoproterenol - pharmacology; Mice; Mice, Knockout; Microscopy, Electron; Myocardial Contraction - drug effects; Myocardial Contraction - physiology; Myocytes, Cardiac - drug effects; Myocytes, Cardiac - metabolism; Myocytes, Cardiac - ultrastructure; Organ Culture Techniques; Sarcoplasmic Reticulum - drug effects; Sarcoplasmic Reticulum - metabolism; Sarcoplasmic Reticulum - ultrastructure; Sodium - metabolism; Sodium-Calcium Exchanger - genetics; Sodium-Calcium Exchanger - metabolism
• ISSN: 0143-4160
• DOI: 10.1016/s0143-4160(03)00018-6

We investigate cardiac excitation-contraction coupling in the absence of sarcolemmal Na(+) - Ca(2+) exchange using NCX1 knock out mice. Knock out of NCX1 is embryonic lethal, and we measure Ca(2+) 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 Ni(2+) and nifedipine block excitation-contraction coupling in NCX-containing (NCX+) and NCX(-/-) heart tubes indicating an essential role for the L-type Ca(2+) current. Under basal conditions (1Hz stimulation), the NCX(-/-) heart tubes have normal Ca(2+) transients but are unable to maintain homeostasis when Ca(2+) 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 Ca(2+), decreased Ca(2+) transient) than the NCX+ heart tubes. Expression of the sarcolemmal Ca(2+) pump was not upregulated. The sarcolemmal Ca(2+) pump, however, was able to compensate surprisingly well for the absence of Na(+) - Ca(2+) exchange under basal conditions.