Inhibition of N‐ and P‐type calcium currents and the after‐hyperpolarization in rat motoneurones by serotonin.

1. We investigated the effects of serotonin (5‐hydroxytryptamine, 5‐HT) on whole‐cell barium currents through calcium channels in visualized neonatal rat hypoglossal motoneurones (HMs) in a thin brainstem slice preparation. 2. High voltage‐activated (HVA) currents were elicited by depolarizing voltage steps from ‐70 to 0 mV; low voltage‐activated (LVA) currents were evoked using steps to between ‐30 and ‐40 mV from hyperpolarized potentials (< ‐80 mV). 5‐HT (1.0 microM) inhibited HVA currents by at least 10% in 70% of HMs tested (n = 99); in those responsive neurones, 5‐HT decreased HVA current by 22 +/‐ 1.3% (mean +/‐ S.E.M.). In contrast, 5‐HT had no effect on LVA current amplitude in HMs (n = 7). 3. Calcium current inhibition was mimicked by 5‐carboxamidotryptamine maleate (5‐CT), a 5‐HT1 receptor agonist, and by R(+)‐8‐hydroxydipropylaminotetralin hydrobromide (8‐OH‐DPAT), a specific 5‐HT1A agonist; N‐(3‐trifluoromethylphenyl) piperazine hydrochloride (TFMPP), a 5‐HT1B agonist, was without effect. The effect of 5‐HT was blocked by the 5‐HT1A antagonist 1‐(2‐methoxyphenyl)‐4‐[4‐(2‐phthalimido)butyl]piperazine hydrobromide (NAN‐190) but not by ketanserin, a 5‐HT2A/2C antagonist. Although R(‐)‐1‐(2,5‐dimethoxy‐4‐iodophenyl)‐2‐aminopropane hydrochloride (DOI), a 5‐HT2A/2C agonist, mimicked the current inhibition by 5‐HT, it was ineffective in the presence of NAN‐190. These data indicate that 5‐HT1A receptors mediate calcium current inhibition by 5‐HT. 4. Following application of either omega‐conotoxin‐GVIA (omega‐CgTX) or omega‐agatoxin‐IVA (omega‐Aga‐IVA), to block N‐ and P‐type components of calcium current, the 5‐HT‐sensitive current was reduced; 5‐HT had no effect on the current remaining after application of both toxins. Thus, 5‐HT inhibits both N‐ and P‐type calcium currents in neonatal HMs. 5. Inhibition of HVA current by 5‐HT was irreversible, and subsequent applications of 5‐HT were occluded, when GTP gamma S was substituted for GTP in the pipette. In addition, inhibition of HVA current by 5‐HT was relieved following depolarizing prepulses. These data indicate that inhibition of calcium channels by 5‐HT is mediated by G proteins. 6. Under current clamp, both 5‐HT and 8‐OH‐DPAT decreased the amplitude of the after‐hyperpolarization (AHP) that followed action potentials, indicating involvement of a 5‐HT1A receptor.(ABSTRACT TRUNCATED AT 400 WORDS)