Effects of Changes in the L-Type Calcium Current on Hysteresis in Restitution of Action Potential Duration

Abstract

Electrical restitution and memory of action potential duration (APD) are considered key determinants of stability of activation. Calcium handling also impacts stability of activation via its modification of the above and independently. We determined the effects of reduction in an important calcium current, I(CaL), on hysteresis in restitution of APD, which provides assessment of restitution and memory. Transmembrane potentials were recorded from isolated ventricular tissues from pigs. The pacing protocols consisted of sequential and oscillatory changes in diastolic intervals (DI). Two protocols were used, one where DIs ranged between 100 and 700 ms and the other where DIs ranged between 10 and 290 ms. Verapamil (2 microM/L) was used to reduce I(CaL). From the hysteresis observed in restitution, loop area, thickness, overall tilt, and the maximum and minimum delays between DIs and APDs were calculated to obtain measures of memory and restitution. Restitution during sequential and oscillatory changes in DI displayed hysteresis. All measures of hysteresis decreased after reduction in I(CaL). The decreases in area, thickness, and overall tilt were most pronounced (50%, 50%, and 33%). Sequential and oscillatory changes in DIs reveal that while the overall slope of restitution of APD decreases with decrease in I(CaL), so do measures of memory. Because slopes and memory are considered to have contrasting effects on stability, our results suggest that predicting effects of alteration in I(CaL) on stability of activation using slope alone may not be adequate. (PACE 2010; 451-459).