<p>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 IAHP and the Ca2+-activated K+ channels mediating the slow IAHP (sIAHP) in hippocampal neurons. Compared with related scorpion toxins, tamapin displayed a unique, remarkable selectivity for SK2 versus SK1 (~1750-fold) and SK3 (~70-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.</p
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