Аннотация
Kv4.3 inactivation is a complex multiexponential process, which can
occur from both closed and open states. The fast component of inactivation
is modulated by the N-terminus, but the mechanisms mediating the
other components of inactivation are controversial. We studied inactivation
of Kv4.3 expressed in Xenopus laevis oocytes, using the two-electrode
voltage-clamp technique. Inactivation during 2000 ms pulses at potentials
positive to the activation threshold was described by three exponents
(46 +/- 3, 152 +/- 13, and 930 +/- 50 ms at +50 mV, n = 7) whereas
closed-state inactivation (at potentials below threshold) was described
by two exponents (1079 +/- 119 and 3719 +/- 307 ms at -40 mV, n =
9). The fast component of open-state inactivation was dominant at
potentials positive to -20 mV. Negative to -30 mV, the intermediate
and slow components dominated inactivation. Inactivation properties
were dependent on pulse duration. Recovery from inactivation was
strongly dependent on voltage and pulse duration. We developed an
11-state Markov model of Kv4.3 gating that incorporated a direct
transition from the open-inactivated state to the closed-inactivated
state. Simulations with this model reproduced open- and closed-state
inactivation, isochronal inactivation relationships, and reopening
currents. Our data suggest that inactivation can proceed primarily
from the open state and that multiple inactivation components can
be identified.
- 16100281
- animals,
- binding,
- biological,
- biology,
- chains,
- channels,
- chemical,
- complementary,
- computational
- computer
- dna,
- electrophysiology,
- extramural,
- factors,
- female,
- gov't,
- kinetics,
- laevis,
- markov
- models,
- n.i.h.,
- non-p.h.s.,
- non-u.s.
- oocytes,
- patch-clamp
- potassium
- protein
- research
- shal
- simulation,
- software,
- structure,,
- support,
- techniques,
- tertiary,
- time
- u.s.
- xenopus
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