The Journal of Neuroscience, March 15, 2002, 22(6):2023-2034
Kurtoxin, A Gating Modifier of Neuronal High- and Low-Threshold
Ca Channels
Serguei S.
Sidach and
Isabelle M.
Mintz
Department of Pharmacology and Experimental Therapeutics, Boston
University Medical Center, Boston, Massachusetts 02118
Studies of Ca channels expressed in oocytes have identified
kurtoxin as a promising tool for functional and structural studies of
low-threshold T-type Ca channels. This peptide, isolated from the
venomous scorpion Parabuthus transvaalicus, inhibits
low-threshold 
1G and 1H Ca channels expressed in oocytes with
relatively high potency and high selectivity. Here we report its
effects on Ca channel currents, carried by 5 mM
Ba2+ ions, in rat central and peripheral neurons. In
thalamic neurons 500 nM kurtoxin inhibited T-type Ca
channel currents almost completely (90.2 ± 2.5% at 
85 mV;
n = 6). Its selectivity, however, was less than
expected because it also reduced the composite high-threshold Ca
channel current recorded in these cells (46.1 ± 6.9% at 30 mV;
n = 6). In sympathetic and thalamic neurons,
250-500 nM kurtoxin partially inhibited N-type and L-type
Ca channel currents, respectively. It similarly reduced the
high-threshold Ca channel current that remains after a blockade of
P-type, N-type, and L-type Ca channels in thalamic neurons. In
contrast, kurtoxin facilitated steady-state P-type Ba currents in
Purkinje neurons (by 34.9 ± 3.7%; n = 10). In all cases the kurtoxin effect was voltage-dependent and entailed a
modification of channel gating. Exposure to kurtoxin slowed current
activation kinetics, although its effects on deactivation varied with
the channel types. Kurtoxin thus appears as a unique gating-modifier
that interacts with different Ca channel types with high affinity. This
unusual property and the complex gating modifications it induces may
facilitate future studies of gating in voltage-dependent ion channels.
Key words:
T-type Ca channel; 
-Aga-IVA; Purkinje neuron; sympathetic neuron; thalamic neuron; high-threshold Ca channel
Copyright © 2002 Society for Neuroscience 0270-6474/02/2262023-12$05.00/0
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