Cysteine sulfinic acid-induced release ofd-[H]aspartate and [C]GABA in hippocampus slices: the role of sodium channels and cAMP

Cysteine sulfinic acid, a putative transmitter in the brain induces release ofd-³H]aspartate and ¹⁴C]GABA without the help of any general depolarizing agent. Tetrodotoxin partially blocks the release ofd-³H]aspartate and completely blocks the induced release of ¹⁴C]GABA. Withdrawal of Ca²⁺ from the medium does not affect thed-³H]aspartate release, but increases the extent of inhibition by tetrodotoxin. In contrast, removal of Ca²⁺ increases the cysteine sulfinic acid-induced ¹⁴C]GABA release, which remains totally blocked by the toxin.Anemonia sulcata toxin type II, which slows down Na⁺ channel inactivation, acts in synergism with cysteine sulfinic acid to increase the rate of release of both of the labeled amino acids. Comparison of glutamate with cysteine sulfinic acid in the same experiments indicates a different action pattern of the two acidic amino acids. Forskolin plus isobutyl methyl xanthine, which are known to raise intracellular cyclic adenosine monophosphate (cyclic AMP) levels, caused little release of the labeled amino acids on their own, but strongly enhanced the cysteine sulfinic acid-induced release. The experiments conducted by double labeling withd-³H]aspartate and ¹⁴C]GABA, revealed several characteristic differences between the glutamatergic and the GABAergic neurons. It is tentatively concluded that cysteine sulfinic acid brings about excitation of the glutamatergic as well as the GABAergic neurons, leading to opening of Na⁺ channels which play a role in the release in both systems. Cyclic AMP, presumably by initiating phosphorylation of a specific component, has a remarkable potentiating effect on the release.