Abstract
Several pathways to neural cell death are involved in ischemic stroke, and all require monovalent or divalent cation influx, implicating non-selective cation (NC) channels. NC channels are also likely to be involved in the dysfunction of vascular endothelial cells that leads to formation of edema following cerebral ischemia. Two newly described NC channels have emerged as potential participants in ischemic stroke, the acid sensing ion channel (ASIC), and the sulfonylurea receptor-1 (SUR1)-regulated NC(Ca-ATP) channel. Non-specific blockers of NC channels, including pinokalant (LOE 908 MS) and rimonabant (SR141716A), have beneficial effects in rodent models of ischemic stroke. Evidence is accumulating that NC channels formed by members of the transient receptor potential (TRP) family are also up-regulated in ischemic stroke and may play a direct role in calcium-mediated neuronal death. The nascent field of NC channels, including TRP channels, in ischemic stroke is poised to provide novel mechanistic insights and therapeutic strategies for this often devastating human condition.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
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Review
MeSH terms
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ATP-Binding Cassette Transporters / metabolism
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ATP-Binding Cassette Transporters / physiology
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Acid Sensing Ion Channels
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Animals
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Brain Ischemia / complications
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Brain Ischemia / genetics
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Brain Ischemia / physiopathology*
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Calcium Channel Blockers / pharmacology
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Calcium-Transporting ATPases / metabolism
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Calcium-Transporting ATPases / physiology
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Humans
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Ion Channels / antagonists & inhibitors
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Ion Channels / genetics
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Ion Channels / physiology*
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Membrane Proteins / genetics
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Membrane Proteins / physiology
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Models, Biological
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Nerve Tissue Proteins / genetics
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Nerve Tissue Proteins / physiology
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Potassium Channels / metabolism
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Potassium Channels / physiology
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Potassium Channels, Inwardly Rectifying / metabolism
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Potassium Channels, Inwardly Rectifying / physiology
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Receptors, Drug / metabolism
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Receptors, Drug / physiology
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Sodium Channels / genetics
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Sodium Channels / physiology
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Stroke / etiology
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Stroke / genetics
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Stroke / physiopathology*
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Sulfonylurea Receptors
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Transient Receptor Potential Channels / genetics
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Transient Receptor Potential Channels / physiology*
Substances
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ABCC8 protein, human
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ATP-Binding Cassette Transporters
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Acid Sensing Ion Channels
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Calcium Channel Blockers
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Ion Channels
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Membrane Proteins
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Nerve Tissue Proteins
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Potassium Channels
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Potassium Channels, Inwardly Rectifying
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Receptors, Drug
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Sodium Channels
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Sulfonylurea Receptors
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Transient Receptor Potential Channels
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non-selective cation channel protein, human
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Calcium-Transporting ATPases