Homozygous Overexpression of the Na: Evidence for Increased Transsarcolemmal Ca2+ Fluxes+: Evidence for Increased Transsarcolemmal Ca2+ Fluxes-Ca: Evidence for Increased Transsarcolemmal Ca2+ Fluxes2+: Evidence for Increased Transsarcolemmal Ca2+ Fluxes Exchanger in Mice: Evidence for Increased Transsarcolemmal Ca2+ Fluxes

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Abstract

ABSTRACT

Mice with homozygous overexpression of the Na+-Ca2+ exchanger (NCX) exhibit threefold levels of NCX expression and an increased Ca2+ extrusion rate. To investigate how Ca2+ homeostasis is maintained in this model, we have characterized Ca2+ influx under these conditions. We find that L-type Ca2+ currents (ICa) inactivate slower due to a reduction of Ca2+-dependent inactivation. Additionally, NCX-overexpressing animals exhibit a prolongation of the action potential (AP). We conclude that transsarcolemmal Ca2+ fluxes in NCX-overexpressing myocytes are balanced by an increase in Ca2+ influx via (a) slowed inactivation of ICa and (b) a prolongation of the AP to compensate for increased Ca2+ efflux.

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