EFFECTS OF SEROTONIN AND CAMP ON CALCIUM CURRENTS IN DIFFERENT NEURONS OF HELIX-POMATIA

Effects of application of serotonin (5-HT) and intracellular administration of cyclic adenosine monophosphate (cAMP) on voltage-gated calcium current (I(ca)) were studied in isolated, intracellularly perfused Helix pomatia neurones. Two types of the effects of 5-HT (1-10-mu-M) were observed in different neurones: reversible inhibition (by about 20%) or reversible potentiation (up to 50%) of the current amplitude. Some cells did not respond to 5-HT application. In cells with the potentiating effect of 5-HT, I(Ca), could also be increased by intracellular introduction of cAMP (100-mu-M), but not the guanosine analogue, cGMP (50-100-mu-M). These effects were not additive and could be potentiated by theophylline (5 mM) and 3-isobutyl-1-methylxanthine (IBMX, 100-500-mu-M); they could be mimicked by forskolin (10-50-mu-M) and abolished by tolbutamide (1-5 mM) or protein kinase inhibitor (500-mu-g/ml), indicating that cAMP-dependent phosphorylation mediates the potentiating action of 5-HT on I(Ca). In neurones showing inhibitory effect of 5-HT, neither cAMP nor forskolin increased I(Ca). Methiothepin (10-50-mu-M), a 5-HT1,2 receptor antagonist, irreversibly inhibited the potentiating effect of 5-HT, while antagonists of 5-HT2 receptors cyproheptadine (10-50-mu-M) or ketanserine (10-60-mu-M) and of 5-HT3 receptors ISC 205 - 930 (10-50-mu-M) or cocaine (5-25-mu-M) had no effect on I(Ca) and its enhancement by 5-HT. It is suggested that in certain snail neurones the possibility of cAMP-dependent up-regulation of I(Ca) correlates with the presence of 5-HT1-like receptors in the neuronal membrane.