Physiological consequences of the P2328S mutation in the ryanodine receptor (RyR2) gene in genetically modified murine hearts.

ABSTRACT:

Aim

To explore the physiological consequences of the ryanodine receptor (RyR2)-P2328S mutation associated with catecholaminergic polymorphic ventricular tachycardia (CPVT).

Methods

We generated heterozygotic (RyR2 p/s) and homozygotic (RyR2 s/s) transgenic mice and studied Ca2+ signals from regularly stimulated, Fluo-3-loaded, cardiac myocytes. Results were compared with monophasic action potentials (MAPs) in Langendorff-perfused hearts under both regular and programmed electrical stimulation (PES).

Results

Evoked Ca2+ transients from wild-type (WT), heterozygote (RyR2 p/s) and homozygote (RyR2 s/s) myocytes had indistinguishable peak amplitudes with RyR2 s/s showing subsidiary events. Adding 100 nm isoproterenol produced both ectopic peaks and subsidiary events in WT

SUBMITTER: Goddard CA 

PROVIDER: S-EPMC2628439 | biostudies-literature | 2008 Oct

REPOSITORIES: biostudies-literature