Abstract
Rapidly inactivating, voltage-dependent K$^+$ currents play important
roles in both neurones and cardiac myocytes. Kv4 channels form the
basis of these currents in many neurones and cardiac myocytes and
their mechanism of inactivation appears to differ significantly from
that reported for Shaker and Kv1.4 channels. In most channel gating
models, inactivation is coupled to the kinetics of activation. Hence,
there is a need for a rigorous model based on comprehensive experimental
data on Kv4.3 channel activation. To develop a gating model of Kv4.3
channel activation, we studied the properties of Kv4.3 channels in
Xenopus oocytes, without endogenous KChIP2 ancillary subunits, using
the perforated cut-open oocyte voltage clamp and two-electrode voltage
clamp techniques. We obtained high-frequency resolution measurements
of the activation and deactivation properties of Kv4.3 channels.
Activation was sigmoid and well described by a fourth power exponential
function. The voltage dependence of the activation time constants
was best described by a biexponential function corresponding to at
least two different equivalent charges for activation. Deactivation
kinetics are voltage dependent and monoexponential. In contrast to
other voltage-sensitive K$^+$ channels such as HERG and Shaker,
we found that elevated extracellular K$^+$ modulated the activation
process by slowing deactivation and stabilizing the open state. Using
these data we developed a model with five closed states and voltage-dependent
transitions between the first four closed states coupled to a voltage-insensitive
transition between the final closed (partially activated) state and
the open state. Our model closely simulates steady-state and kinetic
activation and deactivation data.
- .,
- acid
- action
- active,
- alignment,
- amino
- animals,
- binding
- binding,
- biological
- biological,
- biology,
- calcium
- calcium,
- cardiac,
- cardiovascular,
- chains,
- channel
- channels,
- chemical,
- chloride
- chromatography,
- clocks,
- coli,
- comparative
- complementary,
- computational
- computer
- conductivity,
- data,
- delayed
- dna,
- dynamics,
- electric
- electrophoresis,
- electrophysiology,
- escherichia
- extramural,
- female,
- gating,
- gel,
- gov't,
- high
- homeostasis,
- humans,
- inhibition,
- ion
- kinetics,
- l-type,
- liquid,
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