![Intracellular [Na+] modulates synergy between Na+/Ca2+ exchanger and L-type Ca2+ current in cardiac excitation–contraction coupling during action potentials](https://sim.maxiran.com/images/files/0168863-L-946923229.jpg)
Intracellular [Na+] modulates synergy between Na+/Ca2+ exchanger and L-type Ca2+ current in cardiac excitation–contraction coupling during action potentials
- نوع فایل : کتاب
- زبان : انگلیسی
- مؤلف : Rafael J. Ramirez Rajan Sah Jie Liu Robert A. Rose Peter H. Backx
- چاپ و سال / کشور: 2011
Description
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 (DF/F0) 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 INa as well as SR Ca2? load, which was unchanged under our experimental conditions. However, NCX inhibition using either KB-R7943 or XIP reduced DF/F0 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 ICa,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 ICa,L-mediated ECC
Basic Res Cardiol Received: 11 March 2011 / Revised: 22 June 2011 / Accepted: 4 July 2011
