γ-Aminobutyric acid-induced depression of calcium currents of chick sensory neurons

doi:10.1016/0304-3940(85)90130-2

Neuroscience Letters

Volume 56, Issue 2, 14 May 1985, Pages 205-210

https://doi.org/10.1016/0304-3940(85)90130-2 Get rights and content

Abstract

The effects of γ-aminobutyric acid (GABA) on calcium currents were investigated in avian dorsal root ganglion (DRG) cells. GABA was applied to the vicinity of the cells by ejection pipettes using constant-pressure pulses. GABA concentrations between 5 and 100 μM reduced and slowed the calcium current in a dose-dependent manner. A contribution of K and Cl outward currents to the reduction of the inward current was minimized by using identical caesium chloride concentrations on both sides of the membrane. The onset of the effect was rapid and 80% of the effect was observed within 1 s. The attenuation of the Ca slope conductance by GABA was found to be independent of the membrane potential between −50 and +50 mV.

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GABA activates both ionotropic GABAA receptors (GABAARs) and metabotropic GABABRs. The activation of GABABRs, mediated through inhibitory G-proteins, induces K+-dependent hyperpolarization or slow IPSPs and inhibits voltage-gated calcium currents, which in turn change the transmitter release in both glutamatergic and GABAergic synapses (Chalifoux and Carter, 2011; Deisz and Lux, 1985; Gahwiler and Brown, 1985). GABAB autoreceptors are involved in prolongation of EPSPs and creating conditions required for the activation of the NMDAR currents that trigger LTP (Larson and Lynch, 1986).
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Low-voltage-activated T-type calcium channels are expressed in various tissues, especially in the brain, where they promote neuronal firing and are involved in slow wave sleep and absence epilepsy. While the transduction pathways by which hormones and neurotransmitters modulate high-voltage-activated calcium channels are beginning to be unraveled, those implicated in T-type calcium channel regulation remain obscure. Several neurotransmitters and hormones regulate native T-type calcium channels, although some contradictory data have been reported depending on the cell type studied. This review focuses on the short-term (minutes range) modulation of T-type calcium channels by neurotransmitters and hormones and on the roles of G proteins and protein kinases in these modulatory effects. Results obtained in different native tissues are discussed and compared with the more recent studies of the three cloned T-type calcium channels Ca_V3.1, Ca_V3.2 and Ca_V3.3 in expression systems.
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Locomotor stimulation in response to ethanol in mice may model human ethanol-induced euphoria. The associated neural substrates, possibly relevant to alcoholism, have not been fully elucidated. Systemic injection of baclofen, a GABA_B receptor agonist, attenuates ethanol’s stimulant effects. GABA_B receptors on dopamine cell bodies in the ventral tegmental area (VTA) may modulate ethanol-induced dopamine release, a postulated mechanism for ethanol’s stimulant effects. However, baclofen’s attenuating effects could be associated with peripheral receptor actions. Baclofen was injected i.c.v. or into the VTA of FAST mice, bred for extreme sensitivity to ethanol-induced locomotor stimulation, to test the hypotheses that (1) central GABA_B receptors influence baclofen’s effects on ethanol-stimulated activity, and (2) VTA GABA_B receptors specifically modulate ethanol’s stimulant effects. I.c.v. baclofen dose-dependently attenuated ethanol stimulation, supporting a central locus for baclofen’s effects. Anterior VTA baclofen also attenuated ethanol stimulation. However, more posterior VTA infusions unexpectedly potentiated ethanol stimulation. In SLOW mice, bred for resistance to ethanol stimulation, posterior intra-VTA baclofen did not alter EtOH response. However, anterior VTA baclofen alone produced a locomotor depressant effect in SLOW mice, not seen in FAST mice. GABA_B receptor autoradiography using [³H]CGP 54626, a potent GABA_B receptor antagonist, did not reveal line differences in binding density in the VTA, or in the substantia nigra pars compacta, a nearby brain structure associated with motor control. These results suggest that anterior VTA GABA_B receptors play a role in baclofen’s attenuation of ethanol’s stimulant effects, and that posterior VTA GABA_B receptors serve an opposite role that is normally masked. Selection for differential ethanol stimulant sensitivity has altered VTA GABA_B systems that influence locomotor behavior. However, differences in GABA_B receptor densities in the VTA or substantia nigra pars compacta cannot explain the selected line difference.
GABA<inf>B</inf> receptor-mediated inhibition of mitral/tufted cell activity in the rat olfactory bulb: A whole-cell patch-clamp study in vitro
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GABA, the major inhibitory neurotransmitter involved in information processing in the olfactory bulb, is hypothesized to act through GABA_B receptors by depressing primary neurotransmitter release at the level of olfactory nerve axon endings. The present study was designed to analyze GABA_B receptor-mediated inhibition mechanisms by performing whole-cell patch-clamp recordings of mitral/tufted cell activity in the rat in vitro. To do so, GABA_B receptor-mediated action was mimicked by baclofen and antagonized by saclofen.
Our protocol led us to provide an original description of GABA_B receptor-mediated inhibition exerted on mitral/tufted cells. First, their spontaneous activity was shown to be drastically abolished by baclofen. Second, their responses to olfactory nerve electrical stimulation were graded by GABA_B receptor-mediated inhibition. Indeed, this inhibition may be described as inducing effects ranked from a slight increase in response latency to a complete response suppression.
Altogether, our results corroborate the hypothesis of a presynaptic extrasynaptic GABA_B receptor-mediated inhibition influencing mitral/tufted cell olfactory nerve responsivity. However, the involvement of postsynaptic receptors, with different properties or with different anatomical locations, cannot be ruled out, particularly in the control of spontaneous activity. In conclusion, we underline that, in the vertebrate olfactory bulb, GABA_B receptor-mediated action appears to contribute to make mitral/tufted cell responses more salient by reducing their resting activity.
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GABA_B receptor-mediated responses were investigated in human and rat neocortical neurones in vitro by using intracellular recording. Human epileptogenic tissue and cortex from rats were compared for differences related to the cellular mechanisms of hyperexcitability. In both tissues, single stimuli of various intensities were used to compare basic properties of excitatory and inhibitory postsynaptic potentials (EPSP, IPSP). Paired stimuli, causing a decrease of a second IPSP, were used as an index of presynaptic activation of GABA_B receptors. In neocortical neurones of rats, increasing intensities of stimulation elicited at low intensities (6–8 V) a fairly pure EPSP which was curtailed at higher stimulus intensities (10–14 V) by a GABA_A receptor mediated IPSP (IPSP_A). In all rat neocortical neurones the IPSP_A was followed by a late inhibitory component (IPSP_B, time to peak about 150 ms) which was eliminated by the GABA_B receptor antagonists CGP 35348 or CGP 55845A. On average, paired stimuli reduced the amplitude of a second IPSP_A to 57% of the first (in the presence of 10 μM CNQX and 20 μM D-APV). Paired-pulse depression was only antagonized by CGP 55845A, but not by CGP 35348. The magnitude and time course of paired-pulse depression was markedly enhanced at lower temperatures. In human cortical neurones obtained following epilepsy surgery only low intensity stimuli (4 V) elicited EPSPs. Intermediate to higher stimulus intensities (8–10 V) elicited often all-or-none depolarization shifts or prolonged and increased EPSPs. Few neurones exhibited a sequence of EPSP and IPSPs comparable to that observed in rat neurones. Application of CGP 55845A caused little change in excitability near 150 ms, indicating that the IPSP_B is weak. Paired-pulse depression of inhibition was small in most neurones, the second IPSPA was reduced to 82.8% of the first at a 500 ms interval (n=6). Only two neurones exhibited a paired-pulse depression comparable to rat neurones. The consequences of GABA receptor-mediated paired-pulse depression on neuronal synchronisation are discussed towards the different cellular mechanisms of focal and bilateral synchronous epilepsies.

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Neuroscience Letters

Abstract

References (18)

Control of calcium current in rat sympathetic neurons by norepinephrine

Brain Res.

Pentobarbitone interference with inhibitory synaptic transmission in crayfish stretch receptor neurones

J. Physiol. (Lond.)

Sensory neurones in culture: changing requirements for survival factors during embryonic development

A transient calcium-dependent chloride current in the immature xenopus oocyte

J. Physiol. (Lond.)

Hippocampal seizures and failure of inhibition

Canad. J. Physiol. Pharmacol.

(−)Baclofen decreases neurotransmitter release in the mammalian CNS by an action at a novel GABA receptor

Nature (Lond.)

A low voltage-activated, fully inactivating Ca channel in vertebrate sensory neurones

Nature (Lond.)

Coexistence of GABA_A and GABA_B receptors on Aδ and C primary afferents

Brit. J. Pharmacol.

Two types of γ-aminobutyric acid receptor on embryonic sensory neurones

Brit. J. Pharmacol.

Cited by (115)

The role of CA3 GABA<inf>B</inf> receptors on anxiolytic-like behaviors and avoidance memory deficit induced by D-AP5 with respect to Ca<sup>2 +</sup> ions

GABA <inf>B</inf> receptor coupling to G-proteins and ion channels

Molecular pathways underlying the modulation of T-type calcium channels by neurotransmitters and hormones

Ventral tegmental area region governs GABA <inf>B</inf> receptor modulation of ethanol-stimulated activity in mice

GABA<inf>B</inf> receptor-mediated inhibition of mitral/tufted cell activity in the rat olfactory bulb: A whole-cell patch-clamp study in vitro

GABA(B) receptor-mediated effects in human and rat neocortical neurones in vitro

γ-Aminobutyric acid-induced depression of calcium currents of chick sensory neurons

Abstract

Brain Res.

Pentobarbitone interference with inhibitory synaptic transmission in crayfish stretch receptor neurones

J. Physiol. (Lond.)

Sensory neurones in culture: changing requirements for survival factors during embryonic development

A transient calcium-dependent chloride current in the immature xenopus oocyte

J. Physiol. (Lond.)

Hippocampal seizures and failure of inhibition

Canad. J. Physiol. Pharmacol.

(−)Baclofen decreases neurotransmitter release in the mammalian CNS by an action at a novel GABA receptor

Nature (Lond.)

A low voltage-activated, fully inactivating Ca channel in vertebrate sensory neurones

Nature (Lond.)

Coexistence of GABAA and GABAB receptors on Aδ and C primary afferents

Brit. J. Pharmacol.

Two types of γ-aminobutyric acid receptor on embryonic sensory neurones

Brit. J. Pharmacol.

Coexistence of GABA_A and GABA_B receptors on Aδ and C primary afferents