GABA B -mediated upregulation of the high-voltage-activated Ca 2+ channels in rat dorsal root ganglia

Abstract

The mechanism underlying the enhancement of the high-voltage-activated (HVA) Ca2+ current (ICa) after application of baclofen, a GABAB agonist, in neurones of the rat dorsal root ganglia was studied by a combined use of the nystatin perforated patch clamp recording and our rapid superfusion system. Baclofen (50 microM) decreased the peak amplitude of HVA ICa and slowed the onset of the current, i.e. produced a typical G-protein-mediated inhibition of ICa. However, when baclofen was rapidly removed from the medium, the amplitude of the current was rather augmented, exceeding the control value obtained before application of the drug. This enhancement was not due to a shift of the voltage dependence of Ca2+ channel activation or a change in ionic permeability to other ions. The enhancement of HVA ICa by baclofen was sensitive to pertussis toxin treatment. The enhancement was evident during superfusion of baclofen. Since the inhibitory effect of baclofen on HVA ICa was not attenuated, even after a continuous application of baclofen for 10 min, the enhancement was not due to relief from tonic G-protein-mediated inhibition of the current or a desensitization of the GABAB receptor-effector system. An extremely prolonged time course of the enhancement of HVA ICa by baclofen strongly suggests an involvement of some intracellular signal transduction system.

γ‐Aminobutyric acid type B receptors facilitate L‐type and attenuate N‐type Ca2+ currents in isolated hippocampal neurons

“…Conventionally, it is believed that L‐type channels provide a large contribution to the whole‐cell calcium current at the end of a prolonged depolarizing test pulse. Calcium current facilitation by GABA B receptors has been reported for a number of various cell types (Parramón et al, 1995; Fujikawa et al, 1997; Shen and Slaughter, 1999). In particular, the work of Shen and Slaughter (1999) demonstrated GABA B receptor‐mediated facilitation of L‐type calcium current in salamander retinal neurons.…”

“…Growing evidence supports a facilitatory role for GABA B receptors. For instance, it has been demonstrated in rat dorsal root ganglia neurons that GABA B receptor activation up‐regulates high‐voltage‐activated (HVA) calcium channels (Fujikawa et al, 1997). Additionally, Shen and Slaughter (1999) found that GABA B receptors facilitated current flow through L‐type calcium channels in salamander retinal neurons.…”

Influx of calcium through L‐type calcium channels in early postnatal regulation of chloride transporters in the rat hippocampus

“…Previous experiments in our laboratory have demonstrated facilitation of L-type calcium current by activation of the metabotropic GABA B receptor in acutely cultured hippocampal neurons isolated from 5-7 day old rat pups (Carter and Mynlieff, 2004). Facilitation of L-type calcium current has only been observed in salamander retinal cells (Shen and Slaughter, 1999) and rat dorsal root ganglion cells (Fujikawa et al, 1997), but has not been observed by other investigators studying GABA B receptors using hippocampal tissue from either embryonic or adult rats. The main effect of GABA B receptor activation in adult hippocampus is to decrease N-type calcium current and increase potassium current (Newberry and Nicoll, 1984; Gähwiler and Brown, 1985; Dutar and Nicoll, 1988; Harrison, 1990; Lambert et al, 1991; Scholz and Miller, 1991; Thompson and Gähwiler, 1992; Davies and Collingridge, 1993; Pfrieger et al, 1994; Wu and Saggau, 1995; Takahashi et al, 1998; for review see Bettler et al, 2004).…”

Analgesic α-Conotoxins Vc1.1 and Rg1A Inhibit N-Type Calcium Channels in Rat Sensory Neurons via GABABReceptor Activation

“…The GABA B receptor agonist baclofen has previously been shown to inhibit HVA Ca 2ϩ channel currents in neonatal rat DRG neurons Scott, 1987, 1990;MenonJohansson et al, 1993;Fujikawa et al, 1997). We examined whether the effects of Vc1.1 and baclofen were additive in inhibition of the HVA Ca 2ϩ channel current.…”

“…Numerous studies have shown that activation of GABA B receptors leads to inhibition of N-type Ca 2ϩ channel currents in central and peripheral neurons (Menon-Johansson et al, 1993;Guyon and Leresche, 1995;Fujikawa et al, 1997;Harayama et al, 1998;Richman et al, 2005;Castro et al, 2007;Raingo et al, 2007), but conotoxins have not previously been contemplated to act on this pathway. The inhibition of N-type Ca 2ϩ channel currents after activation of GABA B receptors has been shown to occur in both a voltage-dependent and a voltage-independent manner, to be PTX-sensitive, and to involve c-Src (Richman et al, 2005;Raingo et al, 2007).…”