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Toxins

Staurosporine and K252a Compounds

Protein phosphorylation constitutes one of the most important molecular mechanisms by which extracellular signals produce their biological responses in eukaryotic cells. Stimulation of protein kinases is considered to be the most common activation mechanism in signal transduction systems1. The protein serine/threonine kinase can be classified by the nature of their second messenger activators:

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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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Modulation of Heart Function by Natural Neurotoxins

Cardiac muscle cells (myocytes) are electrically excitable cells, interconnected in groups that respond to stimuli as a unit, contracting together whenever a single cell is stimulated.

Unlike the cells of other muscles and nerves, these cells show a spontaneous, intrinsic rhythm generated by specialized “pacemaker” cells, located in the sinoatrial (SA), and atrioventricular (AV) nodes of the heart. The cardiac cells also have an unusually long action potential, which can be divided into five phases (0 to 4)1,2.

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Large Conductance Ca2+-Dependent K+ (BKCa) Channels

Ca2+ dependent K+ (KCa) channels are divided according to biophysical properties and gene homology into two main groups. KCa were first divided according to their single channel conductance, which represents the speed by which the K+ passes via the open channel. The first group consists of small and intermediate conductance channels (SK and IK respectively, the KCNN gene family). The second group is comprised of large/big conductance channels (called BKCa or maxiK, encoded by the slo or KCNMA1 gene)1.

BKCa channels are both voltage and [Ca2+]in dependent and their response to both signals results in extensive K+ efflux (due to their large single channel conductance) and

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α-Latrotoxin: A Molecular Tool for Induction of Neurotransmitter Release

α-Latrotoxin is a 130 kD protein toxin from the black widow spider venom and is the only protein in the venom that affects mammals (for reviews see references 1,2).

Application of the toxin to presynaptic preparations induces, after a delay, a huge increase in spontaneous neurotransmitter release, which can be evaluated by measuring the postsynaptic response in the form of miniature end plate potentials.

It is widely used to induce and study neurotransmitter release (see Table 1), but the molecular mechanism of its action is not fully determined.

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