Role of slow delayed rectifying potassium current in dynamics of repolarization and electrical memory in swine ventricles

Abstract

Dynamics of repolarization, quantified as restitution and electrical memory, impact conduction stability. Relatively less is known about role of slow delayed rectifying potassium current, I(Ks), in dynamics of repolarization and memory compared to the rapidly activating current I(Kr). Trans-membrane potentials were recorded from right ventricular tissues from pigs during reduction (chromanol 293B) and increases in I(Ks) (mefenamic acid). A novel pacing protocol was used to explicitly control diastolic intervals to quantify memory. Restitution hysteresis, a consequence of memory, increased after chromanol 293B (loop thickness and area increased 27 and 38 %) and decreased after mefenamic acid (52 and 53 %). Standard and dynamic restitutions showed an increase in average slope after chromanol 293B and a decrease after mefenamic acid. Increase in slope and memory are hypothesized to have opposite effects on electrical stability; therefore, these results suggest that reduction and enhancement of I(Ks) likely also have offsetting components that affect stability.

Fig. 1

a An example of sinusoidal DI protocol, with 20 beats of DIs at center value of 400 ms followed by 2 cycles of sinusoidal change ranging from 100 to 700 ms. b Restitution relationship between APD and DI obtained from the DI change shown in (a), which shows two complete hysteresis loops after 20 beats adaptation at center DI. c The second cycle of the DI sequence shown in (a) (solid line) and the resulting APD trace (dashed line). The APD trace is scaled and offset to clearly illustrate maximum delay and minimum delay, which are measured in beats. d Hysteresis loop generated by the second cycle of the DI sequence shown in (a), with illustration of loop thickness, overall tilt and loop area

Fig. 2

An example of transmembrane potentials recorded in one pig at CL of 500 ms which shows the APD differences among control (solid line), chromanol 293B (dashed line), and mefenamic acid (dotted line). APD increased after chromanol 293B and decreased after mefenamic acid

Fig. 3

Standard (a, c) and dynamic (b, d) restitution curves recorded from one trial show the change in slope of restitution after chromanol 293B (a, b) and mefenamic acid (c, d). Slopes in this trial are comparable to the average slopes (n = 6). Slopes of standard and dynamic restitution both increased after chromanol 293B and decreased after mefenamic acid, with more prominent changes in dynamic restitution

Fig. 4

Averaged hysteresis loops (n = 5) during sinusoidal DI protocol with mean DI = 400 ms for control and post-drug. a Control (solid line) versus chromanol 293B (dashed line). b Control (solid line) versus mefenamic acid (dotted line). Curves were shifted vertically (to adjust for differences in APD) in both panels to facilitate comparison between the hysteresis loops

Fig. 5

Averaged hysteresis loops (n = 6) during sinusoidal DI protocol with mean DI of 150 ms for control and post-drug data. As in Fig. 4, the curves were vertically shifted to facilitate comparison between the hysteresis loops