Role of sarcolemmal BK _Ca channels in stretch-induced extrasystoles in isolated chick hearts

Background: It remains unclear whether sarcolemmal BK _Ca channels in post-hatch chick ventricular myocytes contribute to stretch-induced extrasystoles (SIE), and whether they are stretch-activated BK _Ca (SAK _Ca) channels or a non-stretch-sensitive BK _Ca variant. Methods and Results: To determine the role of sarcolemmal BK _Ca channels in SIE and their stretch sensitivity, an isolated 2-week-old Langendorff-perfused chick heart and mathematical simulation were used. The ventricular wall was rapidly stretched by application of a volume change pulse. As the speed of the stretch increased, the probability of SIE also significantly increased, significantly shortening the delay between SIE and the initiation of the stretch. Application of 100 nmol/L of Grammostola spatulata mechanotoxin 4, a cation-selective stretch-activated channel (SAC) blocker, significantly decreased the probability of SIE. The application of Iberiotoxin, however, a BK _Ca channel blocker, significantly increased the probability of SIE, suggesting that a K ⁺ efflux via a sarcolemmal BK _Ca channel reduces SIE by balancing out stretch-induced cation influx via SACs. The simulation using a cardiomyocyte model combined with a new stretch sensitivity model that considers viscoelastic intracellular force transmission showed that stretch sensitivity in BK _Ca channels is required to reproduce the present wet experimental results. Conclusions: Sarcolemmal BK _Ca channels in post-hatch chick ventricular myocytes are SAK _Ca channels, and they have a suppressive effect on SIE.