Properties of the voltage-gated calcium channels mediating dopamine and acetylcholine release from the isolated rat retina

doi:10.1016/0006-8993(95)00053-S

Brain Research

Volume 676, Issue 2, 10 April 1995, Pages 363-370

https://doi.org/10.1016/0006-8993(95)00053-S Get rights and content

Abstract

We examined the properties of voltage-gated calcium channels mediating endogenous dopamine (DA) and acetylcholine (ACh) release in the isolated rat retina. Application of 30 mM KCl elicited the release of DA and ACh, and these releases were abolished in Ca²⁺-free medium. The high K⁺-evoked DA release was largely blocked by both of ω-agatoxin IVA and ω-conotoxin MVIIC, P- and Q-type calcium channel antagonists, and partly blocked by isradipine, an L-type calcium channel antagonist, and ω-conotoxin GVIA, an N-type calcium channel antagonist, ω-Agatoxin IVA at a small dose, sufficient to block P-type channels alone, was however without effect. On the other hand, the high K⁺-evoked ACh release was partly blocked by ω-agatoxin IVA and ω-conotoxin MVIIC, but was resistant to isradipine and ω-conotoxin GVIA. Flunarizine, a non-selective T-type calcium channel antagonist, did not inhibit the release of DA and ACh. Cd²⁺ markedly blocked the release of both DA and ACh, Co²⁺ and Ni²⁺ slightly blocked the release of DA, and the release of ACh was not blocked by these two divalent cations. These results suggest that the high K⁺-evoked release of retinal DA is largely mediated by ω-agatoxin IVA and ω-conotoxin MVIIC sensitive calcium channels (probably Q-type channels), while the release of retinal ACh is largely mediated by as yet uncharacterized Cd²⁺ sensitive calcium channels. The properties of voltage-gated calcium channels involved in the release of ACh in the rat retina differ from those of DA.

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Different neurotransmitter pathways are involved in the therapeutic effectiveness of Pico145. It was reported that a p-type Ca2+ channel blocker w-agatoxin IVA inhibited ACh release from motor nerve endings [58], and the L-type Ca2+ channel blocker isradipine increased ACh release [59]. In studies examining the therapeutic efficacy of ion channel inhibitors, to elucidate the effects of CUMS and the inhibitors administered for therapeutic purposes on neurotransmission, studies that will comprehensively evaluate neurotransmitter levels and the associated receptors are certainly needed.
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This study used the peptides ω-conotoxin GVIA, ω-agatoxin IVA and ω-conotoxin MVIIC, singly and in combination, to investigate the relative involvement of N-, P- and Q-type voltage-operated calcium channels in the control of striatal dopamine release. Electrically stimulated dopamine release was measured by fast cyclic voltammetry at carbon fibre microelectrodes in rat striatal slices. The contribution of these channel subtypes was compared in dorsolateral and medial neostriatum for ‘regular’ (discrete) and ‘burst’ stimulation modalities. In dorsolateral neostriatum, a role for N-, P- and Q-type channels was demonstrated for discrete stimulations, whilst at least one other unidentified channel was also involved in dopamine release on ‘burst’ stimulations. Similarly, in the medial axis of the neostriatum, N-, P- and Q-type channels were involved in dopamine release for discrete stimulations, and N-, Q- and at least one other channel type for ‘burst’ stimulations. However, blockade of P-type channels had no effect on dopamine release for ‘burst’ stimulations in the medial axis. In both regions and stimulation paradigms, N-type channels played a greater role than P/Q-type channels. In the medial axis of the neostriatum there was a smaller contribution by N- and P-type channels and the unidentified component, but a greater Q-type contribution to DA release. ‘Burst’ stimulations induced a lesser involvement of N- and P-type channels than discrete stimulations, and a greater role of the unidentified component. In summary, this study suggests that there is heterogeneity in the distribution of functional voltage-operated calcium channel subtypes in the neostriatum, and differences in subtype recruitment for different firing patterns.
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We characterized the voltage-activated Ca²⁺ channels involved in noradrenaline (NA) release from gastric sympathetic neurons using isolated, vascularly perfused rat stomach. The evoked NA release by electrical stimulation of periarterial nerves was abolished by calcium removal from the perfusion medium and by cadmium. ω-Conotoxin GVIA (N-type Ca²⁺-channel blocker) effectively and ω-conotoxin MVIIC (N/P/Q-type blocker) slightly inhibited the evoked NA, while ω-agatoxin IVA (P-type blocker) had no effect. These results suggest that ω-conotoxin GVIA and ω-conotoxin MVIIC-sensitive N-type Ca²⁺ channels are involved in NA release from the rat gastric sympathetic nerve terminals.
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1998, General Pharmacology
- 1.
  Glutamate is the neurotransmitter released by bipolar cells at their synapses with amacrine cells. The amacrine cells express ionotropic (NMDA, AMPA and kainate) and metabotropic (mGluR1, mGluR2, mGluR4 and mGluR7) glutamate receptors and may take up glutamate from the synaptic cleft.
- 2.
  Activation of the ionotropic glutamate receptors increases the intracellular free calcium concentration ([Ca²⁺]_i), owing to Ca²⁺ entry through the receptor-associated channels as well as through voltage-gated Ca²⁺ channels. The [Ca²⁺]_i response to glutamate may be amplified by Ca²⁺-induced Ca²⁺ release from intracellular sources.
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  Activation of NMDA and non-NMDA glutamate receptors stimulates the release of GABA and acetylcholine from amacrine cells. GABA is released by a Ca²⁺-dependent mechanism and by reversal of the neurotransmitter transporter.
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  Excessive activation of glutamate receptors during ischemia leads to amacrine cell death. An increase in [Ca²⁺]_i due to Ca²⁺ influx through NMDA and AMPA/kainate receptor channels is related to cell death in studies in vitro. In other studies, it was shown that nitric oxide may also take part in the process of cell damage during ischemia.

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Properties of the voltage-gated calcium channels mediating dopamine and acetylcholine release from the isolated rat retina

Abstract

Brain Res.

Neuron

Neuron

Brain Res.

Brain Res.

Neuropharmacology

A study of the factors affecting the aluminum oxide-trihydroxyindole procedure for the analysis of catecholamines

J. Pharmacol. Exp. Ther.

Effect of γ-aminobutyric acid agonist, glycine, taurine and neuropeptides on acetylcholine release from the rabbit retina

J. physiol.

Science

Development of functional calcium channels in cultured avian photoreceptors

Vis. Neurosci.

Investigations of the roles of dihydropyridine and ω-conotoxin-sensitive calcium channels in mediating depolarization-evoked endogenous dopamine release from striatal slices

Naunyn-Schmiedeberg's Arch. Pharmacol.

Blocking and isolation of a calcium channel from neurons in mammals and cephalopods utilizing a toxin fraction (FTX) from funnel-web spider poison

A dihydropyridine-resistant component in the rat adrenal secretory response to splanchnic nerve stimulation

J. Neurochem.

γ-Aminobutyrate type B receptor modulation of L-type calcium channel current at bipolar cell terminals in the retina of the tiger salamander