Synergism between toxin-gamma from Brazilian scorpion Tityus serrulatus and veratridine in chromaffin cells

• Autor(a) principal: Conceição, Isaltino Marcelo da [UNIFESP]
• Data de Publicação: 1998
• Outros Autores: Lebrun, Ivo, Cano-Abad, María, Gandia, Luis, Hernandez-Guijo, Jesus M., Lopez, Manuela G., Villarroya, Mercedes, Jurkiewicz, Aron [UNIFESP], Garcia, Antonio G.
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Institucional da UNIFESP
• Texto Completo: http://ajpcell.physiology.org/content/274/6/C1745; http://repositorio.unifesp.br/handle/11600/42344
• topic: sodium current; catecholamine release; calcium uptake; oscillations of cytosolic calcium

Toxin-gamma (T gamma) from the Brazilian scorpion Tityus serrulatus venom caused a concentration-and time-dependent increase in the release of norepinephrine and epinephrine from bovine adrenal medullary chromaffin cells. T gamma was similar to 200-fold more potent than veratridine judged from EC50 values, although the maximal secretory efficacy of veratridine was 10-fold greater than that of T gamma (1.2 vs. 12 mu g/ml of catecholamine release). The combination of both toxins produced a synergistic effect that was particularly drastic at 5 mM extracellular Ca2+ concentration ([Ca2+](o)), when 30 mu M veratridine plus 0.45 mu M T gamma were used. T gamma (0.45 mu M) doubled the basal uptake of Ca-45(2+), whereas veratridine (100 mu M) tripled it. Again, a drastic synergism in enhancing Ca2+ entry was seen when T gamma and veratridine were combined; this was particularly pronounced at 5 mM [Ca2+](o). Veratridine induced oscillations of cytosolic Ca2+ concentration ([Ca2+](i)) in single fura 2-loaded cells without elevation of basal levels. In contrast, T gamma elevated basal [Ca2+](i) levels, causing only small oscillations. When added together, T gamma and veratridine elevated the basal levels of [Ca2+](i) without causing large oscillations. T gamma shifted the current-voltage (I-V) curve for Na+ channel current to the left. The combination of T gamma with veratridine increased the shift of the I-V curve to the left, resulting in a greater recruitment of Na+ channels at more hyperpolarizing potentials. This led to enhanced and more rapid accumulation of Na+ in the cell, causing cell depolarization, the opening of voltage-dependent Ca2+ channels, and Ca2+ entry and secretion.