Improved Ca²⁺ release synchrony following selective modification of I_tof and phase 1 repolarization in normal and failing ventricular myocytes.

ABSTRACT: Loss of ventricular action potential (AP) early phase 1 repolarization may contribute to the impaired Ca²⁺ release and increased risk of sudden cardiac death in heart failure. Therefore, restoring AP phase 1 by augmenting the fast transient outward K⁺ current (I_tof) might be beneficial, but direct experimental evidence to support this proposition in failing cardiomyocytes is limited. Dynamic clamp was used to selectively modulate the contribution of I_tof to the AP and Ca²⁺ transient in both normal (guinea pig and rabbit) and in failing rabbit cardiac myocytes. Opposing native I_tof in non-failing rabbit myocytes increased Ca²⁺ release heterogeneity, late Ca²⁺ sparks (LCS) frequency and AP duration. (APD)

SUBMITTER: Fowler ED 

PROVIDER: S-EPMC11773631 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature