Guanosine 5'-triphosphate analogue activates potassium current modulated by neurotransmitters in Aplysia neurones.

1. Identified neurones in the abdominal ganglion of Aplysia californica were voltage clamped in order to investigate how guanosine 5'-O-(3-thiotriphosphate) (GTP-gamma-S), a GTP analogue that irreversibly activates guanine nucleotide-binding (G) proteins, modifies activation by the neuropeptide FMRFamide (Phe-Met-Arg-Phe-NH2) of a slow K+ current resembling the serotonin- and adenosine 3',5'-cyclic monophosphate (cyclic AMP)-sensitive 'S' current, and a similar response to acetylcholine. 2. Ionophoretic or pressure injection of GTP-gamma-S into the cell triggered the slow and irreversible development of a large K+ current, rendered the K+ current responses to FMRFamide and acetylcholine irreversible, and finally, once the GTP-gamma-S-induced current had fully developed, occluded the neurotransmitter responses altogether. 3. The K+ currents activated by GTP-gamma-S and acetylcholine had properties identical to those previously found for the FMRFamide-induced 'S'-like K+ current: they were Ca2+ and voltage independent, relatively insensitive to block by extracellular tetraethylammonium (TEA) and 4-aminopyridine (when high concentrations of acetylcholine were used to overcome an additional block by these agents of the receptor), and suppressed in Ba2+-containing solution, by injection of TEA+ or Cs+ into the cell, and by serotonin and elevation of the intracellular concentration of cyclic AMP. 4. The K+ current responses to FMRFamide and acetylcholine were not additive when the agonist concentrations used were high enough to activate most of the available current. 5. Desensitization of either response did not affect the other, and the effect of acetylcholine, but not that of FMRFamide, could be blocked by the known acetylcholine-receptor blockers phenyltrimethylammonium and TEA. 6. These results suggest that FMRFamide and acetylcholine, acting through different receptors, activate the same 'S'-like K+ current by a mechanism involving a G protein. 7. In addition to activating the slow K+ current, FMRFamide and acetylcholine each activate a faster current in these cells, carried by Na+ in the case of FMRFamide, and by Cl- in the case of acetylcholine. Neither fast response was affected by GTP-gamma-S.