Impaired Ca_V1.2 inactivation reduces the efficacy of calcium channel blockers in the treatment of LQT8.

ABSTRACT: Mutations in the Ca_V1.2 L-type calcium channel can cause a profound form of long-QT syndrome known as long-QT type 8 (LQT8), which results in cardiac arrhythmias that are often fatal in early childhood. A growing number of such pathogenic mutations in Ca_V1.2 have been identified, increasing the need for targeted therapies. As many of these mutations reduce channel inactivation; resulting in excess Ca²⁺ entry during the action potential, calcium channel blockers (CCBs) would seem to represent a promising treatment option. Yet CCBs have been unsuccessful in the treatment of LQT8. Here, we demonstrate that this lack of efficacy likely stems from the impact of the mutations on Ca_V1.2 channel inactivation. As CCBs are known to preferentially bind to t

SUBMITTER: Bamgboye MA 

PROVIDER: S-EPMC10583761 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature