Kvβ2 Subunit Regulates Cardiac Levels of SLC41a3 a Sodium‐Magnesium Transporter.

Abstract

BackgroundClinical evidence has demonstrated that administration of magnesium can provide cardioprotective benefits during acute MI as well as suppression of cardiac arrhythmias. Further, meta‐analysis data has uncovered an inverse relation to circulatory levels of magnesium and risk for cardiac injury. Magnesium influx/efflux behaviors have been recorded in isolated cardiomyocytes; further the addition of magnesium during and prior to cardiac injury such as ischemia reperfusion was demonstrated to significantly reduce ischemic injury. While clinical evidence highlights magnesium's cardiovascular benefits, identification and subsequent regulation remain largely unknown of the magnesium channels responsible. Recent research has identified one of the key magnesium/sodium exchange channels as SLC41a1‐3 family. Murine cardiac expression levels demonstrate significant mRNA levels of SLC41a3 in particular.Methods and ResultsA recent microarray study performed in hearts from Kvβ2 knockout mice demonstrated a significant decrease in SLC41a3 mRNA expression compared with control. Protein expression validated the decrease in expression levels of SLC41a3. These findings may indicate the Kvβ2 subunit acts as a novel regulator to SLC41a3, previous research identified Kvβ2 having protein‐protein interactions with SLC39a1 another member of the solute carrier family (SLC). Cardiac function measured by monophasic action potential (AP) recordings presented with a significant reduction in AP duration values in control hearts perfused with magnesium (MgSO4) while Kvβ2 KO hearts demonstrate little to no alterations in AP duration post magnesium exposure. Further functionality will be assessed in isolated cardiomyocytes testing the influx and efflux of magnesium to understand Kvβ2's role in channel activity.HypothesisBased upon our preliminary data we hypothesis that the Kvβ2 subunit plays significant roles in SLC41a3 expression as well as function within the heart.ConclusionThese novel roles of Kvβ2 may shed new light on the molecular understanding of how administration of magnesium can benefit both cardiac injury and arrhythmias.Support or Funding InformationResearch Supported: This Research work was funded by National Institutes of Health (NIH) Grant R01‐HL‐102171 (S. M. Tipparaju).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.