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Duke University Medical Center, Durham, North Carolina 27710
Several aspects of the effect of the KPQ
deletion mutation on Na+ channel
gating remain unresolved. We have analyzed the kinetics of the early
and late currents by recording whole cell and single-channel currents
in a human embryonic kidney (HEK) cell line (HEK293) expressing
wild-type and KPQ deletion mutation in cardiac
Na+ channels. The rate of
inactivation increased three- to fivefold between 
40 and
80 mV in the mutant channel. The rate of recovery from
inactivation was increased twofold. Two modes of gating accounted for
the late current: 1) isolated brief
openings with open times that were weakly voltage dependent and the
same as the initial transient and 2)
bursts of opening with highly voltage-dependent prolonged open times.
Latency to first opening was accelerated, suggesting an acceleration of
the rate of activation. The 
KPQ mutation has multiple effects on
activation and inactivation. The aggregate effects may account for the
increased susceptibility to arrhythmias.
long Q-T syndrome; sodium channel; embryonic kidney cells; patch clamp
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