Crotoxin potentiates L-type calcium currents and modulates the action potential of neonatal rat cardiomyocytes

• Autores: Zhang, Peng; Lader, Alan S.; Etcheverry, Martin A.; Cantiello, Horacio Fabio
• Año de publicación: 2010
• Idioma: inglés
• Tipo de recurso: artículo
• Materia: L-Type Ca2+ Channels; Cardiotoxicity; Cardiac Electrical Activity; Snake Venom; Phospholipase A2
• Institución: Consejo Nacional de Investigaciones Científicas y Técnicas

Crotoxin (CTX), the major component of the venom from the South American rattlesnake (Crotalus durissus terrificus) has diverse toxic effects, including pre-synaptic neurotoxicity. Among these, the effect of CTX in the heart is the least understood. In this study, we explored the effect(s) of CTX on the electrophysiological activity of neonatal rat cardiomyocytes (NRCM). By using patch, voltage-, and current-clamping techniques, we found that, in NRCM, CTX strongly potentiates L-type Ca2+ currents, an important contributor to the cardiac action potential (AP) and excitation-contraction (EC) coupling. External addition of CTX produced a rapid increase in L-type Ca2+ currents. Addition of verapamil (10 μM) an L-type Ca2+ channel blocker, completely blocked the CTX-induced increase in the currents. A detailed kinetic analysis of AP in NRCM revealed that CTX caused both an elongation of AP duration (APD) and an increase of its amplitude, while a decrease of firing frequency. In addition, increasing concentrations of CTX completely blocked the AP as well as the beating of NRCM. The data indicate that CTX is a potent modulator of L-type Ca2+ currents, which provides a possible mechanistic correlation for the cardiotoxicity of the toxin, and may offer potential clinical implications in the control of cardiac function.
Fil: Zhang, Peng. Harvard Medical School; Estados Unidos
Fil: Lader, Alan S.. Harvard Medical School; Estados Unidos
Fil: Etcheverry, Martin A.. Ventech Research; Estados Unidos
Fil: Cantiello, Horacio Fabio. Harvard Medical School; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas (i); Argentina