IONIC BASIS FOR SEROTONIN-INDUCED BISTABLE MEMBRANE-PROPERTIES IN GUINEA-PIG TRIGEMINAL MOTONEURONS

Intracellular recordings and pharmacological manipulations were employ ed to investigate the ionic basis for serotonin-induced bistable membr ane behaviors in guinea pig trigeminal motoneurons (TMNs). In voltage clamp, 10 mu M serotonin (5-HT) induced a region of negative slope res istance (NSR) in the steady-state current-voltage (I-V) relationship a t potentials less negative than -58 mV, creating the necessary conditi ons for membrane bistability. The contributions of sustained Na+ and C a2+ currents to the generation of the NSR were investigated using spec ific ion channel antagonists and agonists. The NSR was eliminated by t he L-type Ca2+ channel antagonist nifedipine (5-10 mu M), indicating t he contribution of L channels. In nifedipine, inward rectification was present in the I-V relationship in a similar voltage range (greater t han -58 mV). This region was subsequently linearized by tetrodotoxin ( TTX),indicating the presence of a persistent Na+ current. When the 5-H T-induced NSR was eliminated by perfusion in low Ca2+ solution (0.4 mM ), it was restored by the Na+ channel agonist veratridine (10 mu M). C ommensurate with bistability, in current clamp during bath application of 5-HT, plateau potentials were elicited by transient depolarizing o r hyperpolarizing stimuli. Plateau potentials evoked by depolarization were observed under control and TTX conditions, but were blocked by n ifedipine, suggesting the participation of an L-type Ca2+ current. Pla teau potentials initiated after release from hyperpolarization (anode break) were blocked by 300 mu M Ni2+, suggesting the responses relied on deinactivation of a T-type Ca2+ current. Conditional bursting was a lso observed in 5-HT. Nifedipine or low Ca2+ solutions blocked burstin g, and the L-channel agonist Bay K 8644 (10 mu M) extended the duratio n of individual bursts, demonstrating the role of L-type Ca2+ currents . Interestingly, when bursting was blocked by nifedipine or low Ca2+, it could be restored by veratridine application via enhancement of the persistent Na+ current. We conclude that bistable membrane behaviors in TMNs are mediated by L-type Ca2+ and persistent Na+ currents. 5-HT is associated with enhancement of TMN activity during oral-motor activ ity; the induction of bistable membrane properties by 5-HT represents a cellular mechanism for this enhancement.