Page 23 - Cardiac Electrophysiology | A Modeling and Imaging Approach

P. 23

Figure 2.9. Conformational changes of K channel during activation. A. Structural basis for two-
+
state voltage-sensor transitions before channel opening. Source: Adapted with permission from
Silverman W et. al. [81] Structural basis of two-stage voltage-dependent activation in K channels.
+
Proc Natl Acad Sci USA. 2003 Mar 4;100(5):2935-40. Copyright (2003), National Academy of
Sciences, U.S.A. B. Kinetic representation of the two-stage voltage-sensor transitions in panel A
(each row represents one of the four α-subunits that form the channel) . First transition is from
80
resting state (R ) to an intermediate state (R ) and second transition from R to an activated state
2
2
1
(A). Once all four voltage sensors are in the activated state, the channel can open. C. There are 15
possible combinations of the four voltage-sensor positions, corresponding to 15 closed states
(C -C ) before channel opening. Blue, red, green indicate a voltage sensor in position R , R , or A,
1
1
2
15
respectively. From Rudy [83]. Reproduced with permission from John Wiley & Sons.
__________________________________________________________________________________________________
from C two transitions are possible, one of the three voltage sensors in R can move to R forming
2 1 2
the C conformation, or R can move to A (green) forming the C conformation, and so on. In this
3 2 6
diagram, horizontal transitions represent movement of the voltage sensors from R to R , while
1 2
vertical transitions represent movements from R to A. When all voltage sensors are in A (C ), a
2 15
cooperative transition can occur to the open state O. Note that voltage sensors in states in the
right column (C , C , C , C ) only have to go through second transitions from R to A before
5 9 12 14 2
channel opening. These transitions are fast (γ=44.7s ) compared to the first transitions from R to R
-1
1 2
(γ =4.45 S ).
-1
The state-diagram of Figure 2.9C is the basis for the I Markov model shown in Figure 2.10A.
Ks
This is an expanded model of the whole channel that includes 15 closed states (an alternative