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Tamapin, a venom peptide from the Indian red scorpion (Mesobuthus tamulus) that targets small conductance Ca2+- activated K+ channels and afterhyperpolarization currents in central neurons

MPS-Authors

Pedarzani,  Paola
Max Planck Institute of Experimental Medicine, Max Planck Society;

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D'Hoedt,  Dieter
Molecular biology of neuronal signals, Max Planck Institute of Experimental Medicine, Max Planck Society;

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Stocker,  Martin
Molecular biology of neuronal signals, Max Planck Institute of Experimental Medicine, Max Planck Society;

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Citation

Pedarzani, P., D'Hoedt, D., Doorty, K. B., Wadsworth, J. D. F., Joseph, J. S., Jeyaseelan, K., et al. (2002). Tamapin, a venom peptide from the Indian red scorpion (Mesobuthus tamulus) that targets small conductance Ca2+- activated K+ channels and afterhyperpolarization currents in central neurons. The Journal of Biological Chemistry, 277(48), 46101-46109.


Cite as: https://hdl.handle.net/11858/00-001M-0000-0029-193A-7
Abstract
The biophysical properties of small conductance Ca2+-activated K+ (SK) channels are well suited to underlie afterhyperpolarizations (AHPs) shaping the firing patterns of a conspicuous number of central and peripheral neurons. We have identified a. new scorpion toxin (tamapin) that binds to SK channels with high affinity and inhibits SK channel-mediated currents in pyramidal neurons of the hippocampus as well as in cell lines expressing distinct SK channel Subunits. This toxin distinguished between the SK channels underlying the apamin- sensitive I-AHP and the Ca2+-activated K+ channels mediating the slow I-AHP (sI(AHP)) in hippocampal neurons. Compared with related scorpion toxins, tamapin displayed a unique, remarkable selectivity for SK2 versus SK1 (similar to1750-fold) and SK3 (similar to70-fold) channels and is the most potent SK2 channel blocker characterized so far (IC50 for SK2 channels = 24 pm). Tamapin will facilitate the characterization of the subunit composition of native SK channels and help determine their involvement in electrical and biochemical signaling.