A caveolae-targeted L-type Ca²+ channel antagonist inhibits hypertrophic signaling without reducing cardiac contractility.

ABSTRACT:

Rationale

The source of Ca(2+) to activate pathological cardiac hypertrophy is not clearly defined. Ca(2+) influx through the L-type Ca(2+) channels (LTCCs) determines "contractile" Ca(2+), which is not thought to be the source of "hypertrophic" Ca(2+). However, some LTCCs are housed in caveolin-3 (Cav-3)-enriched signaling microdomains and are not directly involved in contraction. The function of these LTCCs is unknown.

Objective

To test the idea that LTCCs in Cav-3-containing signaling domains are a source of Ca(2+) to activate the calcineurin-nuclear factor of activated T-cell signaling cascade that promotes pathological hypertrophy.

Methods and results

We developed reagents that targeted Ca(2+) channel-blocking Rem proteins to Cav-3-containing membranes, which hou

SUBMITTER: Makarewich CA 

PROVIDER: S-EPMC3324037 | biostudies-literature | 2012 Mar

REPOSITORIES: biostudies-literature