Contraction (grammar)

Organic chemistry

Myocyte

Biology

Biophysics

Endocrinology

Endoplasmic reticulum

Coupling (piping)

Chemistry

Metallurgy

Materials science

Sodium-calcium exchanger

Calcium

Biochemistry

Intracellular

Basic Research in Cardiology

Excitation–contraction coupling (ECC) in cardiac myocytes involves triggering of Ca2+ release from the sarcoplasmic reticulum (SR) by L-type Ca channels, whose activity is strongly influenced by action potential (AP) profile. The contribution of Ca2+ entry via the Na+/Ca2+ exchanger (NCX) to trigger SR Ca2+ release during ECC in response to an AP remains uncertain. To isolate the contribution of NCX to SR Ca2+ release, independent of effects on SR Ca2+ load, Ca2+ release was determined by recording Ca2+ spikes using confocal microscopy on patch-clamped rat ventricular myocytes with [Ca2+]i fixed at 150 nmol/L. In response to AP clamps, normalized Ca2+ spike amplitudes (ΔF/F 0) increased sigmoidally and doubled as [Na+]i was elevated from 0 to 20 mmol/L with an EC50 of ~10 mmol/L. This [Na+]i-dependence was independent of I Na as well as SR Ca2+ load, which was unchanged under our experimental conditions. However, NCX inhibition using either KB-R7943 or XIP reduced ΔF/F 0 amplitude in myocytes with 20 mmol/L [Na+]i, but not with 5 mmol/L [Na+]i. SR Ca2+ release was complete before the membrane repolarized to −15 mV, indicating Ca2+ entry into the dyad (not reduced extrusion) underlies [Na+]i-dependent enhancement of ECC. Because I Ca,L inhibition with 50 mmol/L Cd2+ abolished Ca2+ spikes, our results demonstrate that during cardiac APs, NCX enhances SR Ca2+ release by synergistically increasing the efficiency of I Ca,L-mediated ECC.

Intracellular [Na+] modulates synergy between Na+/Ca2+ exchanger and L-type Ca2+ current in cardiac excitation–contraction coupling during action potentials