Page 18 - Cardiac Electrophysiology | A Modeling and Imaging Approach

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Figure 2.6. Kinetic transitions of Na+ channels during the guinea pig AP at slow (CL=1000msec,
left) and fast (CL=300msec, right) pacing rate. A. Markovian model of I Na 58 . Channel kinetic states
are color coded: closed-inactivated IC (gray), fast-inactivated IF (purple), slow inactivated IM (green),
closed C (blue), open O (red). B. I , V (top) and occupancy of channel states (bottom) during the
m
Na
first 3msec of the AP at slow rate. There is rapid transition from closed states to the open state,
followed by fast inactivation and transition into the slow inactivated states. Only few channels are
inactivated at AP onset. C. Same as A, but at fast pacing rate. Channels accumulate in the slow in-
activated states (green), which results in reduced I during the AP upstroke and a slower dV /dt max .
m
Na
Reproduced from Rudy and Silva [10], with permission of Cambridge University Press.

Figure 2.6A is a Markov model of I . It includes three closed states (C3, C2, C1), an open state
Na
(O), fast inactivation state (IF), and intermediate and slow inactivated states (IM and IM ). Although
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1
the protein contains four voltage sensors, sodium channel activation is a cooperative process
(movements of the voltage sensors are not independent of each other) that can be modeled by
three closed states, representing putative channel conformations. Fast inactivation occurs
preferentially from the open state (O to IF transitions); IM and IM represent stabilization of
1
2
the inactivated state. IC and IC account for closed-state inactivation, a process that is required
3
2
for correct simulation of channel availability.
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