Ion channels involved in stroke.
Ion channels are membrane proteins that flicker open and shut to regulate the flow of ions down their electrochemical gradient across the membrane and consequently regulate cellular excitability. Every living cell expresses ion channels, as they are critical life-sustaining proteins. Ion channels are generally either activated by voltage or by ligand interaction. For each group of ion channels the channels' molecular biology and biophysics will be introduced and the pharmacology of that group of channels will be reviewed. The in vitro and in vivo literature will be reviewed and, for ion channel groups in which clinical trials have been conducted, the efficacy and therapeutic potential of the neuroprotective compounds will be reviewed. A large part of this article will deal with glutamate receptors, focusing specifically on N-methyl-D-aspartate (NMDA) receptors. Although the outcome of clinical trials for NMDA receptor antagonists as therapeutics for acute stroke is disappointing, the culmination of these failed trials was preceded by a decade of efforts to develop these agents. Sodium and calcium channel antagonists will be reviewed and the newly emerging efforts to develop therapeutics targeting potassium channels will be discussed. The future development of stroke therapeutics targeting ion channels will be discussed in the context of the failures of the last decade in hopes that this decade will yield successful stroke therapeutics.
Institute or Biological Sciences, National Research Council of Canada, Building M-54, 1200 Montreal Road, Ottawa, Ontario, Canada K1A 0R6. dan.small@nrc.ca
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