Abstract
1. The potassium currents evoked by glutamate agonists on isolated and identified neurones of molluscan pedal ganglia were investigated using the voltage clamp technique. 2. Glutamate responses were not modified by increasing intracellular cyclic nucleotide concentrations (treatment with 8-Br-cAMP, 8-Br-cGMP, forskolin and/or the phosphodiesterase inhibitor isobutylmethylxantine, IBMX), whereas inward-going currents induced by the nucleotides were observed. It follows that glutamate currents are independent of intracellular cyclic nucleotide control. 3. Protein kinase C activation with phorbol esters or oleoylacetylglycerol induced a slowly developing outward current and reduced glutamate response amplitude. Staurosporine itself did not affect the glutamate responses but completely prevented the effects of phorbol esters and oleoylacetylglycerol. This indicated that protein kinase C was not involved in the transduction mechanism for the potassium component of the glutamate response. 4. The possible involvement of inositol-1,4,5-trisphosphate seems to be improbable because the glutamate responses were independent of intracellular calcium concentration. Intracellular injection of calcium buffer BAPTA, failed to affect any of the glutamate currents, although it effectively blocked the after-hyperpolarization following directly evoked action potentials. 5. Nordihydroguaiaretic acid (NDGA) and indomethacin, inhibitors of the lipoxygenase and cyclo-oxygenase pathways of arachidonic acid metabolism, correspondingly, did not change the glutamate responses of these neurones. 6. The failure to demonstrate the involvement of any known secondary messenger systems in glutamate response transduction favours two assumptions: (1) the receptor-G protein complex controls the potassium channel directly; or (2) some still unknown transduction system is used.