Respiratory muscle dysfunction may contribute to the symptoms of breathlessness and fatigue in chronic heart failure. Despite this, our understanding of the excitation-contraction coupling process within respiratory muscle remains relatively poor. The diaphragm and respiratory muscles, unlike skeletal muscle, are dependent on an influx of extracellular calcium across the sarcolemmal membrane for their normal function. This influx of calcium requires an active calcium extrusion mechanism, like the Na-Ca exchanger (NCX), to facilitate relaxation.We have investigated the expression of different NCX isoforms in diaphragmatic muscle obtained from a rabbit coronary artery ligation model of chronic heart failure. Sham operated rabbits served as controls and all procedures were performed in accordance with the Animals (Scientific Procedures) Act, 1986. The animals were killed by a lethal overdose of sodium pentobarbital (100mg/kg). We used quantitative PCR to examine gene expression and western blotting to examine protein expression but found no difference in NCX isoform mRNA or protein levels between the two groups (antibody p11-13 was obtained from Swant, Switzerland).We further investigated the effect of the NCX inhibitor KB-R7943 (Tocris, USA) on the twitch and tetanic force generated in isolated phrenic nerve stimulated arterially perfused hemidiaphragm preparations from ligated rabbits and controls. Twitch and tetanic force was reduced from baseline by similar amounts in the two groups in a dose dependent manner. For example, 20µM KBR reduced twitch force by 57.9±8.8% in control vs 57.5±3.9% in ligated (n = 5 in each group, P<0.001 student t-test). Tetanic force was reduced by 36.4±14.6% in control vs 42.4±7.6% in ligated animals (n = 5 in each group, P<0.001 student t-test). All data are mean±SEM.These data are consistent with suggestion that calcium influx through the NCX operating in reverse mode contributes to muscle activation in the normal rabbit diaphragm. Coronary artery ligation does not alter NCX expression or its function in the diaphragm.