The Role Of The Sodium Calcium Exchanger In Excitation-Contraction Coupling

Date
2013-09-24
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Abstract
Numerous studies on single cardiomyocytes have attempted to charecterize the role of the Na+/Ca2+ exchanger (NCX) in Excitation-Contraction Coupling (ECC). Some reports suggest that sodium accumulation in the dyadic cleft early in the cardiac action potential may allow the NCX work in the reverse mode to allow for calcium entry. In this way the NCX has been suggested to be important in the early triggering of calcium release from the Sarcoplasmic Reticulum (SR) as well as in frequency-dependent positive inotropy. Contradictory reports, however, have suggested that any calcium-entry through the NCX is of negligible magnitude to influence these properties of ECC. Part of this discrepancy is thought to arise from the sensitivity of the NCX to the surrounding biochemical milieu. The purpose of these studies was to investigate the role of the NCX in ECC in intact muscle preparations to preserve near-in vivo physiological conditions. This was accomplished by using cardiac trabeculae that were excised from the right ventricle of the rat and exposed to the novel NCX inhibitor SEA0400. Parameters such as twitch force, sarcomere length and intracellular calcium ([Ca2+]int) were measured. NCX inhibition was found to increase both the calcium transient amplitude and twitch force, however the kinetics of relaxation for both parameters were unchanged. Furthermore, the fraction of activating calcium that recirculated back into the SR (RF) was found to increase. These results are in accordance with inhibition of sarcolemmal calcium extrusion via the NCX. NCX inhibition had no effect on the latency from stimulus to the onset of calcium release. The latency to sarcomere length shortening and force generation, however, was diminished. In addition, NCX inhibition helped facilitate the early recovery of the cardiac twitch, as assessed by mechanical restitution curves. This suggests that there is no significant calcium entry through the NCX during the early cardiac action potential. Furthermore, inhibition of the NCX enhanced the maximum rate of relaxation of the calcium transient and force production without changing the time course of relaxation or the time constant of the exponential decay. These results suggest cardiac relaxation is not NCX-dependent. Rather, in ECC the NCX works primarily as a calcium extrusion mechanism that helps to set the total amount of calcium stored in the SR.
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Physiology
Citation
de Vries, E. (2013). The Role Of The Sodium Calcium Exchanger In Excitation-Contraction Coupling (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca. doi:10.11575/PRISM/28363