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Intracellular [Na(+)] modulates synergy between Na(+)/Ca (2+) exchanger and L-type Ca (2+) current in cardiac excitation-contraction coupling during action potentials.

Authors: Ramirez, RJ  Sah, R  Liu, J  Rose, RA  Backx, PH 
Citation: Ramirez RJ, etal., Basic Res Cardiol. 2011 Nov;106(6):967-77. doi: 10.1007/s00395-011-0202-z. Epub 2011 Jul 21.
Pubmed: (View Article at PubMed) PMID:21779914
DOI: Full-text: DOI:10.1007/s00395-011-0202-z

Excitation-contraction coupling (ECC) in cardiac myocytes involves triggering of Ca(2+) release from the sarcoplasmic reticulum (SR) by L-type Ca channels, whose activity is strongly influenced by action potential (AP) profile. The contribution of Ca(2+) entry via the Na(+)/Ca(2+) exchanger (NCX) to trigger SR Ca(2+) release during ECC in response to an AP remains uncertain. To isolate the contribution of NCX to SR Ca(2+) release, independent of effects on SR Ca(2+) load, Ca(2+) release was determined by recording Ca(2+) spikes using confocal microscopy on patch-clamped rat ventricular myocytes with [Ca(2+)](i) fixed at 150 nmol/L. In response to AP clamps, normalized Ca(2+) spike amplitudes (DeltaF/F (0)) increased sigmoidally and doubled as [Na(+)](i) was elevated from 0 to 20 mmol/L with an EC(50) of ~10 mmol/L. This [Na(+)](i)-dependence was independent of I (Na) as well as SR Ca(2+) load, which was unchanged under our experimental conditions. However, NCX inhibition using either KB-R7943 or XIP reduced DeltaF/F (0) amplitude in myocytes with 20 mmol/L [Na(+)](i), but not with 5 mmol/L [Na(+)](i). SR Ca(2+) release was complete before the membrane repolarized to -15 mV, indicating Ca(2+) entry into the dyad (not reduced extrusion) underlies [Na(+)](i)-dependent enhancement of ECC. Because I (Ca,L) inhibition with 50 mmol/L Cd(2+) abolished Ca(2+) spikes, our results demonstrate that during cardiac APs, NCX enhances SR Ca(2+) release by synergistically increasing the efficiency of I (Ca,L)-mediated ECC.

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RGD Object Information
RGD ID: 8554732
Created: 2014-05-08
Species: All species
Last Modified: 2014-05-08
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.