Autoradiographic localization of N-type VGCCs in gerbil hippocampus and failure of ω-conotoxin MVIIA to attenuate neuronal injury after transient cerebral ischemia

Azimi-Zonooz, Aryan; Kawa, Chad; Dowell, Cheryl; Olivera, Baldomero M.

doi:10.1016/s0006-8993(01)02471-4

Cited by 16 publications

(8 citation statements)

References 44 publications

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“…Localization studies on Ca v 2.2 channels using autoradiography of the Cv2.2-specific 125 I-labelled-GIVA-conotoxin (149) in mammalian brain revealed high-density expression in neuronal synaptic terminals in the striatum, hippocampus, cortex, and cerebellum (3, 9, 148, 320, 321). Higher resolution analyses in the hippocampus revealed intense 125 I-ω-GIVA-conotoxin-binding signals in regions rich in axons and presynaptic terminals, mainly in the CA3 s. lucidum where mossy fiber axons and terminals are located (9). Strong 125 I-ω-GIVA-conotoxin-binding signals were also detected in the infragranular polymorphic region of the dentate gyrus, and s. radiatum and s. lacunosum moleculare of CA1, which contains the Schaffer collateral, and lateral perforant path, axons and nerve terminals (9).…”

Section: Voltage-dependent Calcium Channel Localizationmentioning

confidence: 99%

“…Higher resolution analyses in the hippocampus revealed intense 125 I-ω-GIVA-conotoxin-binding signals in regions rich in axons and presynaptic terminals, mainly in the CA3 s. lucidum where mossy fiber axons and terminals are located (9). Strong 125 I-ω-GIVA-conotoxin-binding signals were also detected in the infragranular polymorphic region of the dentate gyrus, and s. radiatum and s. lacunosum moleculare of CA1, which contains the Schaffer collateral, and lateral perforant path, axons and nerve terminals (9). Immunolocalization studies using a Ca v 2.2-specific antibody yielded similar results with strong immunoreactivity in punctate/synaptic structures in rat brain (356).…”

Section: Voltage-dependent Calcium Channel Localizationmentioning

confidence: 99%

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Localization and Targeting of Voltage-Dependent Ion Channels in Mammalian Central Neurons

Vacher

Mohapatra²,

Trimmer

2008

Physiological Reviews

444

469

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The intrinsic electrical properties and the synaptic input-output relationships of neurons are governed by the action of voltage-dependent ion channels. The localization of specific population of ion channels with distinct functional properties at discrete sites in neurons dramatically impacts excitability and synaptic transmission. Molecular cloning studies have revealed a large family of genes encoding voltage-dependent ion channel principal and auxiliary subunits, most of which are expressed in mammalian central neurons. Much recent effort has focused on determining which of these subunits co-assemble into native neuronal channel complexes, and the cellular and subcellular distributions of these complexes, as a crucial step in understanding the contribution of these channels to specific aspects of neuronal function. Here we review progress made on recent studies aimed at determining the cellular and subcellular distribution of specific ion channel subunits in mammalian brain neurons using in situ hybridization, and immunohistochemistry. We also discuss the repertoire of ion channel subunits in specific neuronal compartments and implications for neuronal physiology. Finally, we discuss the emerging mechanisms for determining the discrete subcellular distributions observed for many neuronal ion channels. I. OVERVIEW OF MAMMALIAN BRAIN VOLTAGE-DEPENDENT ION CHANNELS A. IntroductionMammalian central neurons express a large repertoire of voltage-dependent ion channels (VDICs) that form selective pores in the neuronal membrane and confer diverse properties of intrinsic neuronal excitability. This allows mammalian neurons to display a richness of firing behaviors over a wide range of stimuli and firing frequencies. The complex electrical behavior of mammalian neurons is due to a huge array of VDICs with distinct ion flux rates and selectivity, although the major VDICs underlying neuronal excitability and electrical signaling are those selective for Na + , K + and Ca 2+ ions. Neuronal VDICs also exhibit widely differing properties of how sensitive their gating, or the opening or closing of the channels pore, is to changes in membrane potential. Different VDICs also differ in the kinetics of these gating events. Importantly in the terms of mammalian brain, different VDICs differ widely in their cellular expression and subcellular localization, impacting their relative contribution to brain

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Section: Voltage-dependent Calcium Channel Localizationmentioning

confidence: 99%

Section: Voltage-dependent Calcium Channel Localizationmentioning

confidence: 99%

Localization and Targeting of Voltage-Dependent Ion Channels in Mammalian Central Neurons

Vacher

Mohapatra²,

Trimmer

2008

Physiological Reviews

444

469

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“…Ziconotide has also been tested for neuroprotection [22,23] where its efficacy has been tested against ischaemic stroke and in coronary bypass surgery. However these human neuroprotection trials have been disappointing and have been abandoned [24]. More recently, other conopeptides with analgesic activity have been identified in the venom of the fish-eating cone, Conus catus [25], and the molluscivorous cones, Conus marmoreus [26] and Conus victoriae [1].…”

Section: Conus -A Rich Source Of Pharmacolo-gically Active Peptidesmentioning

confidence: 99%

Drugs from the Sea: Conopeptides as Potential Therapeutics

Livett¹,

Gayler²,

Khalil³

2004

Current Medicinal Chemistry

158

149

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Marine cone snails from the genus Conus are estimated to consist of up to 700 species. These predatory molluscs have devised an efficient venom apparatus that allows them to successfully capture polychaete worms, other molluscs or in some cases fish as their primary food sources. The toxic venom used by the cone shells contains up to 50 different peptides that selectively inhibit the function of ion channels involved in the transmission of nerve signals in animals. Each of the 700 Conus species contains a unique set of peptides in their venom. Across the genus Conus, the conotoxins represent an extensive array of ion channel blockers each showing a high degree of selectivity for particular types of channels. We have undertaken a study of the conotoxins from Australian species of Conus that have the capacity to inhibit specifically the nicotinic acetylcholine receptors in higher animals. These conotoxins have been identified by mass spectroscopy and their peptide sequences in some cases deduced by the application of modern molecular biology to the RNA extracted from venom ducts. The molecular biological approach has proven more powerful than earlier protein/peptide based technique tor the detection of novel conotoxins [1,2]. Novel conotoxins detected in this way have been further screened for their abilities to modify the responses of tissues to pain stimuli as a first step in describing their potential as lead compounds for novel drugs. This review describes the progress made by several research groups to characterise the properties of conopeptides and to use them as drug leads for the development of novel therapeutics for the treatment of a range of neurological conditions.

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“…6 VSCCs are almost entirely restricted to neurons, where they play a major role in the release of synaptic mediators (secondary to Ca 2+ influx) such as glutamate, acetylcholine, dopamine, norepinephrine, gammaaminobutyric acid (GABA), and calcitonin-gene-related peptide (CGRP). 7 Their role in the release of glutamate, GABA, and CGRP makes these channels important in pain perception.…”

Section: Voltage-sensitive Calcium Channels and Painmentioning

confidence: 99%

Ziconotide: Can we use it in palliative care?

Prommer

2005

Am J Hosp Palliat Care

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Ziconotide (PRIALT) is a new nonopioid treatment for chronic pain. It is a peptide that is the synthetic analog of the omega-conotoxin, derived from the marine snail, Conus magus. The therapeutic benefit of ziconotide derives from its potent and selective blockade of neuronal N-type voltage-sensitive calcium channels. Interference with these channels inhibits input from pain-sensing primary nociceptors. A recent clinical trial demonstrated that ziconotide has a significant analgesic effect compared to placebo in patients considered intolerant or refractory to other treatment such as systemic analgesics, adjunctive therapies, or intrathecal (IT) morphine. Thus, ziconotide is the first of a new class of agents--N-type calcium channel blockers, or NCCBs. Ziconotide may represent another option for patients with refractory pain.

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Autoradiographic localization of N-type VGCCs in gerbil hippocampus and failure of ω-conotoxin MVIIA to attenuate neuronal injury after transient cerebral ischemia

Cited by 16 publications

References 44 publications

Localization and Targeting of Voltage-Dependent Ion Channels in Mammalian Central Neurons

Localization and Targeting of Voltage-Dependent Ion Channels in Mammalian Central Neurons

Drugs from the Sea: Conopeptides as Potential Therapeutics

Ziconotide: Can we use it in palliative care?

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