Serotonergic Inhibition of the T-Type and High Voltage-Activated Ca²⁺Currents in the Primary Sensory Neurons ofXenopusLarvae

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 Ca 2ϩ currents. In ϳ80% of the acutely isolated R-B neurons, 5-HT inhibited the high voltage-activated (HVA) currents by 16% (n ϭ 29) and the T-type currents by 24% (n ϭ 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 -conotoxin-GVIA (N-type channel blocker), whereas the rest of the modulation (ϳ30%) was occluded by Ͻ100 nM -agatoxin-TK (P/Q-type channel blocker). This suggests that 5-HT acts on N-and P/Q-type Ca 2ϩ 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 Ca 2ϩ 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.

Mechanisms and significance of reduced activity and responsiveness in resting frog tadpoles

“…Neurons containing 5-HT are present in the raphe nucleus of stage 37/38 tadpoles (Van Mier et al, 1986) and 5-HT has been shown to block initiation of swimming by both skin stimulation and dimming (Sillar and Simmers, 1994;Jamieson, 1997). 5-HT inhibition of responsiveness to skin stimulation involves presynaptic inhibition of primary afferent neurons (Sillar and Simmers, 1994) and an increase in their firing threshold (Sun and Dale, 1997). This presynaptic action of 5-HT contrasts with the postsynaptic action of GABAergic inhibition on spinal CPG neurons during the stopping response (Li et al, 2003) and, as we now propose, during attachment.…”

Paclitaxel-induced epithelial damage and ectopic MMP-13 expression promotes neurotoxicity in zebrafish

“…The epidermis is separated from the underlying rudimentary dermis by a basement membrane. DRG neurons are not functional until ∼4 wk when the epidermis stratifies, and initially axons of unmyelinated Rohonbeard (RB) neurons with analogy to mammalian C-fibers (20) innervate the skin and arborize between both layers. To assess RB axon degeneration in transgenic Tg(isl2b:GFP) (21) (Fig.…”

Pharmacology of currents underlying the different firing patterns of spinal sensory neurons and interneurons identified in vivo using multivariate analysis

“…7). Because amiloride blocks low-voltage-activated T-type calcium channels (Fox et al 1987;Tang et al 1988), this suggests currents carried by T-type channels contribute to depolarization in stage 37/38 RB neurons; such a role has been reported in Xenopus RB neurons at stage 42 (Sun and Dale 1997). In DL neurons, amiloride also affected depolarization, greatly reducing the AP peak and the rate of depolarization (Table 4 and Fig.…”