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

Am J Physiol. 1998 Jun;274(6):C1745-54. doi: 10.1152/ajpcell.1998.274.6.C1745.

Abstract

Toxin-gamma (Tgamma) 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. Tgamma was approximately 200-fold more potent than veratridine judged from EC50 values, although the maximal secretory efficacy of veratridine was 10-fold greater than that of Tgamma (1.2 vs. 12 microg/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 microM veratridine plus 0.45 microM Tgamma were used. Tgamma (0.45 microM) doubled the basal uptake of 45Ca2+, whereas veratridine (100 microM) tripled it. Again, a drastic synergism in enhancing Ca2+ entry was seen when Tgamma 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, Tgamma elevated basal [Ca2+]i levels, causing only small oscillations. When added together, Tgamma and veratridine elevated the basal levels of [Ca2+]i without causing large oscillations. Tgamma shifted the current-voltage (I-V) curve for Na+ channel current to the left. The combination of Tgamma 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenal Medulla / drug effects
  • Adrenal Medulla / physiology*
  • Animals
  • Calcium / metabolism
  • Calcium / pharmacology
  • Calcium Channel Blockers / pharmacology
  • Calcium Channels / physiology
  • Calcium Radioisotopes
  • Cattle
  • Chromaffin System / drug effects
  • Chromaffin System / physiology*
  • Drug Synergism
  • Electric Conductivity
  • Kinetics
  • Neurotoxins / pharmacology*
  • Norepinephrine / metabolism
  • Scorpion Venoms / pharmacology*
  • Sodium Channels / physiology
  • Veratridine / pharmacology*

Substances

  • Calcium Channel Blockers
  • Calcium Channels
  • Calcium Radioisotopes
  • Neurotoxins
  • Scorpion Venoms
  • Sodium Channels
  • tityustoxin
  • Veratridine
  • Calcium
  • Norepinephrine