Z16b, a natural compound from Ganoderma cochlear is a novel RyR2 stabilizer preventing catecholaminergic polymorphic ventricular tachycardia.

ABSTRACT: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited, lethal ventricular arrhythmia triggered by catecholamines. Mutations in genes that encode cardiac ryanodine receptor (RyR2) and proteins that regulate RyR2 activity cause enhanced diastolic Ca²⁺ release (leak) through the RyR2 channels, resulting in CPVT. Current therapies for CPVT are limited. We found that Z16b, a meroterpenoid isolated from Ganoderma cochlear, inhibited Ca²⁺ spark frequency (CaSF) in R2474S/ + cardiomyocytes in a dose-dependent manner, with an IC₅₀ of 3.2 μM. Z16b also dose-dependently suppressed abnormal post-pacing Ca²⁺ release events. Intraperitoneal injection (i.p.) of epinephrine and caffeine stimulated sustained ventricular tachycardia in all R

SUBMITTER: Wan JF 

PROVIDER: S-EPMC9433431 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature