Page 83 - YORAM RUDY BOOK FINAL

P. 83
Figure 3.6. Role of I Ca,L in propaga- A
tion during reduced excitability.
A. SF with (solid line) or without
(dashed line) contribution from
I Ca,L . SF without I Ca,L begins to
diverge from SF with I Ca,L below
30% of sodium channel availability.
B. AP upstrokes for conduction
at highly reduced excitability (20%
sodium channel availability), with
(solid line) or without (dashed line)
I Ca,L . Inset bar graph shows relative
charge Q (current integrated over
time) generated by I (Q ) and by
Na
Na
I Ca,L (Q Ca(L) ) during the period from a
given cell’s excitation (0 msec) to
excitation of its downstream
adjoining cell (marked by thin
vertical line at time = 0.37 msec). B
Even for this severe I suppression,
Na
charge contribution by I to
Na
support conduction far exceeds
charge contribution from I Ca,L ,
and conduction is predominantly
maintained by I . From Shaw
Na
and Rudy [174], with permission
from Wolters Kluwer Health, Inc.

(decrease in extracellular and intracellular pH), and anoxia (decrease of intracellular ATP, [ATP] ).
i
We applied these conditions to the model fiber in different combinations and with varying degrees
of severity; results are shown in Figure 3.7A, 209 together with corresponding experimental data in
Figure 3.7B. 205 Simulated conditions included changes in [K ] alone (solid curve) or in combination
+
0
with acidosis (dashed curve). dV /dt max , an index of membrane excitability, is shown as a function
m
of conduction velocity for a range of [K ] . As [K ] is raised from an initial value of 3mM, there is very
+
+
0
0
little change in dV /dt max but conduction velocity increases to a maximum value. The maximum
m
velocity is achieved at [K ] =8.2 mM in the absence of acidosis and [K ] =8.0mM in its presence. This
+
+
0
0
initial transient increase of conduction velocity is termed “supernormal conduction.” It results from
depolarization of the membrane rest potential due to the elevated [K ] , without significant sodium
+
0
channel inactivation at this range of negative potentials (hence the almost constant dV /dt max ).
m
The elevation of the rest potential reduces the amount of depolarizing charge needed to reach
excitation threshold, which increases conduction velocity. As [K ] increases further, the higher
+
0
membrane depolarization leads to significant sodium channel inactivation and reduced availability.