Cardiac function is regulated by the sodium-dependent inhibition of the sodium-calcium exchanger NCX1.

ABSTRACT: The Na⁺-Ca²⁺ exchanger (NCX1) is the dominant Ca²⁺ extrusion mechanism in cardiac myocytes. NCX1 activity is inhibited by intracellular Na⁺ via a process known as Na⁺-dependent inactivation. A central question is whether this inactivation plays a physiological role in heart function. Using CRISPR/Cas9, we inserted the K229Q mutation in the gene (Slc8a1) encoding for NCX1. This mutation removes the Na⁺-dependent inactivation while preserving transport properties and other allosteric regulations. NCX1 mRNA levels, protein expression, and protein localization are unchanged in K229Q male mice. However, they exhibit reduced left ventricular ejection fraction and fractional shortening, while displaying a prolonged QT interval. K22

SUBMITTER: Scranton K 

PROVIDER: S-EPMC11076594 | biostudies-literature | 2024 May

REPOSITORIES: biostudies-literature