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 biophysical properties of small conductance Ca(2+)-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 Ca(2+)-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 ( approximately 1750-fold) and SK3 ( approximately 70-fold) channels and is the most potent SK2 channel blocker characterized so far (IC(50) 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.
Pedarzani
Paola
P
Department of Physiology, University College London, London WC1E 6BT, United Kingdom.
D'hoedt
Dieter
D
Doorty
Kevina B
KB
Wadsworth
Jonathan D F
JD
Joseph
Jeremiah S
JS
Jeyaseelan
Kandiah
K
Kini
R Manjunatha
RM
Gadre
S V
SV
Sapatnekar
S M
SM
Stocker
Martin
M
Strong
Peter N
PN
D000595:Amino Acid Sequence; D000818:Animals; D001030:Apamin / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D006801:Humans; D008564:Membrane Potentials / Q000187:drug effects*; D008969:Molecular Sequence Data; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D009498:Neurotoxins / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D012604:Scorpion Venoms / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D012605:Scorpions; D017386:Sequence Homology, Amino Acid; D021241:Spectrometry, Mass, Electrospray Ionization
D009498:Neurotoxins; D015221:Potassium Channels; D012604:Scorpion Venoms; C000597457:tamapin peptide, Mesobuthus tamulus; D001030:Apamin; D002118:Calcium