Actions of baclofen on components of the Ca‐current in rat and mouse DRG neurones in culture

Abstract

1 Ca currents in rat and mouse sensory dorsal root ganglion (DRG) neurones were inhibited by concentrations of (-)-baclofen as low as 1^i . The proportion of neurones responding to baclofen was low (< 20%), except in young cultures of neonate rat DRG neurones (3 days in culture), where 86% of the neurones were responsive. 2 Three types of unitary Ca currents were observed in the rat DRG neurones, corresponding to the T-, N-and L-type currents of chick DRG neurones. 3 Baclofen produced two types of response on whole-cell currents of DRG neurones from both species. The first was on an early inactivating component of the Ca current. This early current was partially inactivated at a holding potential of -40mV. It was also reduced during the second of a pair of depolarizing command pulses. The results suggest that this action of baclofen is due to an action on an N-type component of the current. The second response to baclofen persisted throughout the command step and was not reduced during the second of a pair of command pulses, indicating that this effect is due to an action on the L-type current. 4 Unitary or ensemble Ca currents recorded in cell-attached patches, on neurones previously shown to respond to baclofen in whole-cell clamp mode, were generally not inhibited by baclofen application external to the patch electrode. This indicates that a readily diffusible internal second messenger substance is probably not involved in coupling the GABAB receptor to the ion channels.

GABAB receptors inhibit low-voltage activated and high-voltage activated Ca2+ channels in sensory neurons via distinct mechanisms

“…There are also number of other pathways by which GPCR can inhibit VGCC, including phosphatidylinositol 4,5-bisphosphate (PIP2 depletion) [41,42], arachidonic acid [43] and Src kinase [15]. Inhibition of T-type channels by GABAB receptors in DRG neurons has been reported [44] but the mechanism of inhibition (and particularly if it is the same as for the inhibition of HVA currents) has not been investigated. We report that in cultured small-diameter rat DRG neurons GABAB receptor agonist baclofen inhibits both HVA and LVA currents (by ~32% and ~22% respectively) but the mechanisms of inhibition are at least partially different.…”

G protein-coupled inwardly rectifying potassium channels in dorsal root ganglion neurons

“…The GABA B receptor has also been reported to be present in DRG neurons and play important physiological roles [14,28,29] , and to modulate N-type calcium channels through G(o) pathways [14,[28][29][30] . GABA inhibits peptide secretion through the activation of GABA B receptors that are functionally coupled to pertussis toxin-sensitive G proteins in peripheral sensory neurons from embryonic chick DRG [31] .…”

Modulation of pain transmission by G-protein-coupled receptors

“…Because prior blockade of N-type Ca 2+ channels with ω-conotoxin-GVIA completely occludes baclofen-induced inhibition of VGCCs, the N-type Ca 2+ current appears to be mainly responsible for the inhibition of VGCCs by baclofen. Application of GABA or baclofen shortens the DRG action potential duration by decreasing an N-type Ca 2+ current (Green and Cottrell, 1988). Reduction in GABA B1 receptor subunit with antisense oligodeoxynucleotide substantially attenuates the inhibitory effect of baclofen on VGCCs, indicating that the GABA B1 subunit contributes to baclofen-induced inhibition of VGCCs in DRG neurons (Hand et al, 2000).…”