Hodgkin-Huxley and partially coupled inactivation models yield different
voltage dependence of block.
Am. J. Physiol., 272 (4 Pt 2):
H2013--H2022 (April 1997)Abstract
K$^+$ channel blockers have been shown to exhibit complex time-
and voltage-dependent effects on cardiac K$^+$ currents. Whereas
much attention has been focused on the state dependence of K$^+$
channel block, how a particular channel model can alter the predicted
time and voltage dependence of channel block remains unexplored.
In this study, using two different model formalisms for the same
cardiac transient outward current channel, we compare the effects
of a theoretical open-state specific channel blocker on macroscopic
currents. Model 1 is a Hodgkin-Huxley-like model, in which inactivation
is an intrinsically voltage-dependent process and occurs independently
of activation. Model 2 is a "partially coupled" model, in which inactivation
is intrinsically voltage insensitive but requires channel activation
before it can proceed. In the absence of drug (blocking agent), the
two models reproduce the macroscopic current data. In the presence
of blocking agent, the two models can differ substantially, with
model 1 displaying much less block than model 2. We also examine
simple mathematically convenient modifications to the Hodgkin-Huxley
formalism, which reproduce some, but not all, of the use-dependent
properties of block. Thus model formalism is important for analysis
and simulation of state-specific drug-channel interactions.
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