Action Potential Repolarization in Equine Hearts

Abstract

The heart rate in horses can vary between 30 and 250 beats per minute. This suggests an important role for a dynamic regulation of the repolarizing potassium currents.Methods and Results: Kv7.1 and KCNE1 that underlie the slow delayed rectifying current (IKs) as well as Kv11.1 and KCNE2 that underlie the rapid delayed rectifying current (IKr) were cloned from equine hearts. All subunits exhibit a high degree of homology with their human variants. Co-expression of equine Kv7.1 and KCNE1 in Xenopus laevis oocytes revealed a current with overall properties similar to the human Kv7.1/KCNE1 complex, however, the voltage dependence of activation was significantly right shifted (V1/2, equine=51.7 mV and V1/2, human=26.4 mV) and the deactivation was slower (Tauequine=1288 and Tauhuman=613 ms). Equine Kv11.1 and KCNE2 current kinetics were similar to those of the human variants and the channel complex was susceptible to pharmacological block by terfenadine. To address the functional role of IKr and IKs in equine hearts, we recorded action potentials from arterially-perfused wedge preparations from the right ventricular wall at different pacing rates. In the presence of 10 μM terfenadine a marked prolongation of the action potential duration (from 420 ms to 495 ms at 90% of repolarization (APD90) at a basic cycle length of 2000 ms) was observed.Conclusions: The expression of Kv7.1 and Kv11.1 in equine hearts suggests as in humans they are important for cardiac repolarization and we have demonstrated a functional role for IKr in equine hearts. The slower activation of equine IK7.1/KCNE1 may be an adaption to long action potential duration at rest and the slower deactivation may lead to current accumulation during fast rates and thus be important for decreasing action potential duration at faster heart rates.