Page 81 - YORAM RUDY BOOK FINAL

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Figure 3.5. AP propagation during reduced membrane excitability. Conduction velocity (solid line)
and safety factor (SF) of conduction (dashed line) decrease monotonically as excitability is reduced.
Horizontal black bars indicate conduction failure, which occurs when SF falls below 1. The slowest
velocity attainable before conduction failure is 17 cm/sec. From Shaw and Rudy [174], with
permission from Wolters Kluwer Health, Inc.

An important observation can be made from the results of figure 3.5. The slowest
conduction velocity of successful propagation is 17 cm/sec (further decrease of excitability results
in conduction failure). This velocity is only reduced by a factor of 3 relative to normal conduction at
full excitability (54 cm/sec in the simulated fiber). This observation brings us to the conclusion that

reduced membrane excitability cannot support very slow conduction. In fact, it leads to an abrupt
transition to conduction failure from propagation that is relatively fast. This quantitative prediction
of the model is consistent with experimental observations. Elevation of extracellular potassium

depolarizes the resting membrane potential, which leads to sodium channels inactivation and
reduced excitability. Experimental elevation of [K ] caused an abrupt conduction failure from
+
o
velocities of 10-35 cm/sec. 202,205 Similarly, abrupt failure of conduction was observed with drug block
of I (from velocities of ~ 25 cm/sec) 200 and during I suppression by acute ischemia (from
Na Na
velocities of 20-30 cm/sec). 202,205

In normal myocardium with full excitability, I provides the depolarizing current that
Na
generates the action potential upstroke and supports conduction. The question should be asked

whether when I is suppressed, this is still the case. It is conceivable that the L-type calcium
Na