MedWire News: Researchers have shown cardiac expression and biologic effects of the CAPON protein, supporting its potential influence on QT interval variation in human populations.

Rare disease-causing mutations leading to congenital long- or short-QT syndrome are well recognized, but the basis for QT interval variation in normal populations remains unclear, explain Eduardo Marbán and colleagues from Johns Hopkins University in Baltimore, Maryland, USA.

The researchers previously identified a link between the CAPON gene and QT interval length in a German population.

However, CAPON has previously only been characterized in brain tissue where it functions as a neuronal nitric oxide synthase (NOS)1 regulator.

To investigate its potential role in cardiac physiology further, Marbán and team looked for endogenous CAPON protein expression in animal heart tissue.

As reported in an advance online publication by the Proceedings of the National Academy of Sciences, the team detected CAPON protein expression in extracts of guinea pig ventricular myocardium.

Using an adenoviral vector system to overexpress the CAPON gene in myocytes, the researchers then showed that increased levels of the protein accelerated action potentials. Mean action potential durations (APDs) were significantly shortened at 1 Hz stimulation in CAPON-overexpressing myocytes compared with control myocytes.

Further analysis showed that this APD acceleration was the result of upregulation of NOS1-NO pathways and consequent suppression of L-type calcium channel currents and augmentation of the rapidly activating component of outward rectifier potassium channel currents.

The researchers conclude: "Our findings provide a rationale for the association of CAPON gene variants with extremes of the QT interval in human populations."

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