Serotonergic inhibition of the T-type and high voltage-activated Ca2+ currents in the primary sensory neurons of Xenopus larvae

Abstract

The primary sensory Rohon-Beard (R-B) neurons of Xenopus larvae are highly analogous to the C fibers of the mammalian pain pathway. We explored the actions of 5-HT by studying the modulation of Ca2+ currents. In ~80% of the acutely isolated R-B neurons, 5-HT inhibited the high voltage- activated (HVA) currents by 16% (n = 29) and the T-type currents by 24% (n = 41). The modulation of the T-type and the HVA currents was mimicked by selective 5-HT(1A) and 5-HT(1D) agonists: 8-OH-DPAT and L-694,247. The effects of the agonists were blocked by their respective 5-HT(1A) or 5- HT(1D) antagonists: p-MPPI and GR127935, suggesting that both 5-HT(1A) and 5- HT(1D) receptors were involved. Approximately 70% of the actions of 5-HT on HVA currents was occluded by ω-conotoxin-GVIA (N-type channel blocker), whereas the rest of the modulation (~30%) was occluded by <100 nM ω- gatoxin-TK (P/Q-type channel blocker). This suggests that 5-HT acts on N- and P/Q-type Ca2+ channels. Neither the modulation of the T-type nor that of the HVA currents was accompanied by changes in their voltage-dependent kinetics. Cell-attached patch-clamp recordings suggest that the modulation of the T-type channel occurs through a membrane-delimited second messenger. We have studied the functional consequences of the modulation of T-type Ca2+ channels and have found that these channels play a role in spike initiation in R-B neurons. Modulation of T-type channels by 5-HT therefore could modulate the sensitivity of this sensory pathway by increasing the thresholds of R-B neurons. This is a new and potentially important locus for modulation of sensory pathways in vertebrates.