Page 31 - YORAM RUDY BOOK FINAL

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Figure 2.17 highlights the species dependence of the AP. The top row in each panel shows
experimental recordings and the bottom panel corresponding simulations with ORd . The
91
92
protocols involve block of I or I , simulating effects of drugs or mutations. For 70% I block (Fig
Kr
Kr
Ks
2.17A), simulated APD was substantially prolonged in the human (77%, 172 ms APD prolongation).
Block consequence was comparatively small for dog (34%, 65 ms APD prolongation), rabbit (32%,
67 ms APD prolongation) and guinea pig (21%, 35 ms APD prolongation). In Fig. 2.17B, 90% I
Ks
block was essentially of no consequence for human (4%, 10 ms APD prolongation), dog (1%, 2ms
APD prolongation) and rabbit (3%, 8 ms APD prolongation). By contrast, only 50% I block (right
Ks
panels) was required to substantially prolong APD in guinea pig (27%, 44 ms APD prolongation).

Simulated application of the ß-agonist isoproterenol increased the effect of I block for human
Ks
and dog (not shown ), but the effects still remained smaller than in guinea pig.
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Figure 2.17. Species dependence
A of delayed rectifiers block. A: I
Kr
block. B: I block. Results from
Ks
human, dog, rabbit and guinea pig
are shown from left to right. Shown
are steady state APs at CL=1,000
ms for control and K current block.
+
Experiments from Jost et al.
91
are shown above simulations.
Simulated block levels were chosen
to match experiments. From Jost
et al. [91], courtesy of Promenade
A Publishing House, Budapest,
Hungary and from O’Hara and
Rudy [92] courtesy of The American
Physiological Society.

B