Article Publish Status: FREE
Abstract Title:

Calcitriol, the Bioactive Metabolite of Vitamin D, Increases Ventricular KCurrents in Isolated Mouse Cardiomyocytes.

Abstract Source:

Front Physiol. 2018 ;9:1186. Epub 2018 Aug 24. PMID: 30197603

Abstract Author(s):

María Tamayo, Laura Martin-Nunes, Almudena Val-Blasco, Maria J Piedras, María J Larriba, Nieves Gómez-Hurtado, María Fernández-Velasco, Carmen Delgado

Article Affiliation:

María Tamayo


Calcitriol, the bioactive metabolite of vitamin D, interacts with the ubiquitously expressed nuclear vitamin D receptor (VDR) to induce genomic effects, but it can also elicit rapid responses via membrane-associated VDR through mechanisms that are poorly understood. The down-regulation of Kcurrents is the main origin of electrophysiological remodeling in pathological hypertrophy and heart failure (HF), which can contribute to action potential prolongation and subsequently increase the risk of triggered arrhythmias. Adult mouse ventricular myocytes were isolated and treated with 10 nM calcitriol or vehicle for 15-30 min. In some experiments, cardiomyocytes were pretreated with the Akt inhibitor triciribine. In the adult mouse ventricle, outward Kcurrents involved in cardiac repolarization are comprised of three components: the fast transient outward current (I), the ultrarapid delayed rectifier Kcurrent (I), and the non-inactivating steady-state outward current (I). Kcurrents were investigated using the whole-cell or the perforated patch-clamp technique and normalized to cell capacitance to obtain current densities. Calcitriol treatment of cardiomyocytes induced an increase in the density of Iand I, which was lost in myocytes isolated from VDR-knockout mice. In addition, calcitriol activated Akt in cardiomyocytes and pretreatment with triciribine prevented the calcitriol-induced increase of outward Kcurrents. In conclusion, we demonstrate that calcitriol via VDR and Akt increases both Iand Idensities in mouse ventricular cardiomyocytes. Our findings may provide new mechanistics clues for the cardioprotective role of this hormone in the heart.

Study Type : Animal Study

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