Loss of K+ currents in heart failure is accentuated in KChIP2 deficient mice.

Søren Grubb, Tobias Speerschneider, Dona Occhipinti, Céline Fiset, Søren-Peter Olesen, Morten B Thomsen, Kirstine Calloe

Journal of cardiovascular electrophysiology 2014 Aug

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KV 4 together with KV Channel-Interacting Protein 2 (KChIP2) mediate the fast recovering transient outward potassium current (I(to,f)) in the heart. KChIP2 is downregulated in human heart failure (HF), potentially underlying the loss of I(to,f). We investigated remodeling associated with HF hypothesizing that KChIP2 plays a central role in the modulation of outward K(+) currents in HF. HF was induced by aortic banding in wild-type (WT) and KChIP2 deficient (KChIP2(-/-)) mice, evaluated by echocardiography. Action potentials were measured by floating microelectrodes in intact hearts. Ventricular cardiomyocytes were isolated and whole-cell currents were recorded by patch clamp. Left ventricular action potentials in KChIP2(-/-) mice were prolonged in a rate dependent manner, consistent with patch-clamp data showing loss of a fast recovering outward K(+) current and upregulation of the slow recovering I(to,s) and I(Kur). HF decreased all outward K(+) currents in WT mice and did not change the relative contribution of I(to,f) in WT mice. Compared to WT HF, KChIP2(-/-) HF had a larger reduction of K(+) -current density. However, the relative APD prolongation caused by HF was shorter for KChIP2(-/-) compared with WT, and the APs of the 2 HF mouse types were indistinguishable. I(to,f) is just one of many K(+) currents being downregulated in murine HF. The downregulation of repolarizing currents in HF is accentuated in KChIP2(-/-) mice. However, the prolongation of APs associated with HF is less in KChIP2(-/-) compared to WT, suggesting other compensatory mechanism(s) in the KChIP2(-/-) mouse. © 2014 Wiley Periodicals, Inc.

Citation

Søren Grubb, Tobias Speerschneider, Dona Occhipinti, Céline Fiset, Søren-Peter Olesen, Morten B Thomsen, Kirstine Calloe. Loss of K+ currents in heart failure is accentuated in KChIP2 deficient mice. Journal of cardiovascular electrophysiology. 2014 Aug;25(8):896-904