Cf. Hsiao et al., IONIC BASIS FOR SEROTONIN-INDUCED BISTABLE MEMBRANE-PROPERTIES IN GUINEA-PIG TRIGEMINAL MOTONEURONS, Journal of neurophysiology, 79(6), 1998, pp. 2847-2856
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.