Notch-Mediated Epigenetic Regulation of Voltage-Gated Potassium Currents.

ABSTRACT:

Rationale

Ventricular arrhythmias often arise from the Purkinje-myocyte junction and are a leading cause of sudden cardiac death. Notch activation reprograms cardiac myocytes to an induced Purkinje-like state characterized by prolonged action potential duration and expression of Purkinje-enriched genes.

Objective

To understand the mechanism by which canonical Notch signaling causes action potential prolongation.

Methods and results

We find that endogenous Purkinje cells have reduced peak K⁺ current, I_to, and I_K,slow when compared with ventricular myocytes. Consistent with partial reprogramming toward a Purkinje-like phenotype, Notch activation decreases peak outward K⁺ current density, as well as the outward K⁺ cu

SUBMITTER: Khandekar A 

PROVIDER: S-EPMC5148677 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature