Comparative actions of synthetic omega -grammotoxin SIA and synthetic omega -Aga-IVA on neuronal calcium entry and evoked release of neurotransmitter in vitro and in vivo

• Published in: Neuropharmacology Vol. 34; no. 11; pp. 1515 - 1528
• Main Authors: Keith, R A, Mangano, T J, Lampe, R A, DeFeo, P A, Hyde, MJ, Donzanti, BA
• Format: Journal Article
• Language: English
• Published: 01.01.1995
• ISSN: 0028-3908

The effects of synthetic omega -grammotoxin SIA ( omega -GsTx SIA) and synthetic omega -Aga-IVA were tested in in vitro and in vivo neurochemical assays that are reflective of voltage-sensitive calcium channel function. Synthetic omega -GsTx SIA inhibited K super(+)-evoked rat and chick synaptosomal super(45)Ca super(2+) flux, K super(+)-evoked release of [ super(3)H]D-aspartate and [ super(3)H]norepinephrine from rat hippocampal brain slices and K super(+)-evoked release of [ super(3)H]norepinephrine from chick cortical brain slices with potency values that were comparable to those found previously with omega -GsTx SIA purified from the venom of the tarantula spider Grammostola spatulata. These results indicate that trace contaminants do not account for the pharmacology of purified omega -GsTx SIA. omega -GsTx SIA caused a complete inhibition of rat synaptosomal super(45)Ca super(2+) flux and hippocampal slice [ super(3)H]D-aspartate release, whereas omega -Aga-IVA caused a maximal inhibition of approx 75%. omega -GsTx SIA and omega -Aga-IVA caused an identical partial inhibition of K super(+)-evoked increases of intracellular calcium in cortical neurons in primary culture. The addition of nitrendipine to either omega -GsTx SIA or omega -Aga-IVA resulted in an additive and virtually complete inhibition of the cortical neuron intracellular calcium response. In in vivo microdialysis studies, the K super(+)-evoked release of glutamate from hippocampus of awake freely moving rats was inhibited with the following rank order of potency: omega -conotoxin GVIA> omega -GsTx SIA> omega -Aga-IVA. Complete inhibition of K super(+)-evoked hippocampal glutamate release was observed with 300 nM omega -conotoxin GVIA and 3 mu M omega -GsTx SIA. In urethane anesthetized rats, omega -CgTx GVIA caused a partial inhibition, whereas omega -GsTx SIA caused a concentration-dependent and complete inhibition, of basal serotonin release in the hippocampus. Therefore, omega -GsTx SIA was shown to inhibit responses that are sensitive to omega -conotoxin GVIA, omega -Aga-IVA and omega -conotoxin MVIIC, consistent with the notion that omega -GsTx SIA inhibits N-, P- and Q-type high threshold voltage-sensitive calcium channels.