Hodgkin-huxley and partially coupled models of inactivation predict
different voltage dependence of block.
Liu, Shuguang, and Randall L. Rasmusson.
aDepartment of Medicine, Duke University Medical Center, Box 3845
Durham, NC 27710, USA; bDepartment of Biomedical Engineering, Room
136, School of Engineering, Box 90281, Duke University, Durham, NC
27708, USA
APStracts 3:0513H, 1996.
K+ channel blockers have been shown to exhibit complex time- and
voltage-dependent effects on cardiac K+ currents. While 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 we compare the effects of a theoretical open-state specific
channel blocker on macroscopic currents using two different model
formalisms for the same cardiac Ito channel. 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 convienient 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.
Received 3 June 1996; accepted in final form 15 November 1996.
APS Manuscript Number H499-6.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 31 December 1996