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Issue No. 14

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Role of Voltage-Gated K+ Channels in the Pathophysiology of Spinal Cord Injury

Spinal cord injury (SCI) is a devastating condition afflicting over 13,000 people annually in North America and is an important cause of mortality and neurological morbidity1.

Although early pharmacological intervention after SCI with methylprednisolone2,3 or GM-1 ganglioside4 results in modest neurological improvement, the overall impact of these treatments remains minimal. Therefore, novel therapeutic approaches are required to improve the neurological outcome of these patients.

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Molecular Diversity of P2 Receptors

ATP is released into the extracellular milieu upon cell and tissue damage, secretory exocytosis or activation of plasma membrane transporters.

Many types of excitatory or non-excitatory cells maintain specific receptors to ATP or other nucleotides on their surface. Nucleotide receptors, also named P2, in contrast to P1 adenosine receptors, comprise two different families: ionotropic P2X receptors and metabotropic P2Y receptors.

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Dendrotoxins: Powerful Blockers of Voltage-Gated K+ Channels

Dendrotoxins are a family of 7 kDa. homologous polypeptides isolated from both green and black mamba venoms (Dendroaspis sp.)1-3. They contain 57-61 amino acid residues in a single chain, crosslinked by three disulfide bridges. Several Dendrotoxins have been isolated and their amino acid sequences completely (see Table 1) , while β- and γ-Dendrotoxin have only been partially sequenced1-4.

Dendrotoxins were first discovered to facilitate the release of acetylcholine at the neuromuscular junction4,5. Later discoveries demonstrated their ability to selectively block some voltage-dependent K+ channels in nerve endings with high affinity2,5.

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GABAA receptors

GABA (γ-aminobutyric acid) is the essential inhibitory neurotransmitter in the vertebrate brain. It interacts with three kinds of receptors: Class …

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