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Scorpion Toxin Block of the Early K + Current ( I Kf ) in Rat Dorsal root Ganglion Neurones
Author(s) -
Matteson Donald R.,
Blaustein Mordecai P.
Publication year - 1997
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1111/j.1469-7793.1997.285bh.x
Subject(s) - depolarization , charybdotoxin , dorsal root ganglion , chemistry , biophysics , time constant , washout , stereochemistry , membrane potential , anatomy , dorsum , biochemistry , physics , biology , engineering , electrical engineering , meteorology
1 The ability of three structurally homologous scorpion toxins to block voltage‐dependent K + currents in rat dorsal root ganglion neurones was examined using the patch‐clamp technique. 2 Neurones with a diameter > 35 μm had two identifiable components of macroscopic K + current. The outward current during depolarizations had both inactivating and non‐inactivating components, and the tail currents had both a fast component ( I Kf ) with a time constant of about 2.5 ms and a slow component ( I Ks ) with a time constant of about 10 ms. 3 The functional properties of I Kf and I Ks differed in several ways: (i) I Kf activated over a more negative voltage range than I Kf ; (ii) I Kf partially inactivated during a depolarization to +70 mV, whereas I Ks did not inactivate during a 1 s depolarization to +70 mV; (iii) I Kf activated more rapidly than I Ks ;and (iv)α‐dendrotoxin selectively blocked I Kf . 4 Tityustoxin‐Kα (TsTX‐Kα) selectively blocked I Kf , with little or no effect on I Ks . The block was concentration dependent, with 50% of the current inhibited at a toxin concentration of about 38nM. 5 TsTX‐Kα block of I Kf was completely reversible, but the washout rate was slow. The time constant of recovery from TsTX‐Kα block was about 11 min. 6 Charybdotoxin (CTX) also selectively blocked I Kf in a reversible manner, but was about 10 times less potent than TsTX‐Kα. The CTX washout rate was over 10 times faster than that of TsTX‐Kα; the time constant of recovery was 0.8 min. 7 Pandinotoxin‐Kα (PiTX‐Kα) also selectively blocked I Kf ; the IC 50 for block of I Kf was about 8.1nM. In contrast to the other two toxins, however, PiTX‐Kα was poorly reversible. 8 The block of I Kf produced by CTX was voltage dependent. In the voltage range from ‐10 to +70 mV, the fraction of blocked I Kf fell from 91 to 37%. In contrast, both TsTX‐Kα and PiTX‐Kα blocked I Kf in a voltage‐independent manner. 9 The backbone structure and many of the amino acid side‐chains on the presumed docking surfaces of the toxins are identical or conservatively replaced in all three toxins. Thus, some small differences in a few side‐chains that influence electrostatic, hydrophobic/hydrophilic and/or steric interactions probably account for the marked differences in affinities and dissociation rates.