Species Specific Effect of Omega-Conotoxin on Intracellular Calcium Levels

摘要

Omega-Conotoxin GVIA (CgTx), a component of the venom of the piscivorus snail Conus geographus is an extremely potent inhibitor of Calcium (++) channels. Significant inhibition of voltage stimulated Ca++ channel (VSCC) influx has been reported at micromolar and lower concentrations. We have examined the effects of this toxin on the regulation of intracellular Ca++ levels in rat and chicken brain synaptosomes and in primary cultures of mouse cortical neurons. The intracellular concentration of free ionized Ca++ was monitored using the Ca++ sensitive dye, FURA-2. With this technique, very small changes in free intracellular Ca++ levels were easily detected. Ca++ concentrations in synaptosomes from either chicken or rat synaptosomes or mouse cortical neurons were not significantly different from each other. Similarly, the response of these neuronal preparations to depolarizing stimuli (K+) was very similar. However, the effects of CgTx on the VSCC's was very different among the preparations. In rat brain synaptosomal preparations, doses of CgTx up to and including 5 micromoles, had no discernible effect on the response of the VSCC to depolarizing concentrations of K+ (21.66 mM final). Intracellular free Ca++ concentrations rose markedly during the period immediately following the depolarizing stimulus, typically a 1.5 to 2-fold increase, in a manner identical to that in control synaptosomes. In chicken synaptosomes on the other hand, CgTx in doses from 0.1 to 1 micromole caused a dose-dependent reduction in the rise of intracellular Ca++ levels in response to K+. Canada. (AW)