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Journal of Neuroscience, Vol 4, 2836-2842, Copyright © 1984 by Society for Neuroscience
Voltage clamp analysis of sodium channels in normal and scorpion toxin- resistant neuroblastoma cells
T Gonoi, B Hille and WA Catterall
Sodium currents mediated by voltage-sensitive sodium channels in normal and
scorpion toxin-resistant neuroblastoma cells were measured using a giga-ohm
seal recording method in the whole cell patch configuration. The voltage
and time dependence of sodium currents were similar in normal and mutant
cell lines. Half-maximal activation occurred for test depolarizations in
the range of -7 to -11 mV. Half-maximal inactivation occurred for
pre-pulses in the range of -62 to -69 mV. Scorpion toxin from Leiurus
quinquestriatus (100 to 200 nM) increased the time constant for sodium
channel inactivation 6- to 9-fold, increased the peak sodium current 2.0
+/- 0.5-fold, shifted the voltage dependence of sodium channel activation 7
to 11 mV to more negative potentials, and made the voltage dependence of
inactivation less steep. These effects were observed for both normal and
scorpion toxin-resistant neuroblastoma cells. However, the effect of
Leiurus toxin on the rate of inactivation was half-maximal at 1.7 nM for
the parental cell line N18, in contrast to 5.4 or 39 nM for the scorpion
toxin-resistant clone LV30 and 24 or 51 nM for LV10. These results show
that scorpion toxin resistance results from a specific change in channel
properties that does not impair normal function but causes an increase in
the apparent KD for Leiurus toxin action on sodium channels.
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