Potential role of cardiac calsequestrin in the lethal arrhythmic effects of cocaine.

ABSTRACT:

Background

Cocaine-related deaths are continuously rising and its overdose is often associated with lethal cardiotoxic effects.

Methods and results

Our approach, employing isothermal titration calorimetry (ITC) and light scattering in parallel, has confirmed the significant affinity of human cardiac calsequestrin (CASQ2) for cocaine. Calsequestrin (CASQ) is a major Ca(2+)-storage protein within the sarcoplasmic reticulum (SR) of both cardiac and skeletal muscles. CASQ acts as a Ca(2+) buffer and Ca(2+)-channel regulator through its unique Ca(2+)-dependent oligomerization. Equilibrium dialysis and atomic absorption spectroscopy experiments illustrated the perturbational effect of cocaine on CASQ2 polymerization, resulting in substantial reduction of its Ca(2+)-binding capacit

SUBMITTER: Sanchez EJ 

PROVIDER: S-EPMC4097383 | biostudies-literature | 2013 Dec

REPOSITORIES: biostudies-literature