Abstract 1521: A Transmural Gradient of the Task-1 Channel Exists Across the Left Ventricular Wall
The twin-pore K+ channel, TASK-1, acts as an open-rectifying K+-selective pore at the resting membrane potential. We previously showed TASK-1 protein expression at the intercalated discs, and as a striated pattern within single ventricular myocytes. This study investigates our hypothesis that across the left ventricular wall, a transmural gradient exists for TASK-1 current (ITASK) and TASK-1 channel protein. Whole cell patch clamp electrophysiology measured ITASK in isolated single left ventricular rat myocytes. Epicardial myocytes (3.5±0.74pA, mean ± S.E.M.) possessed 45% less ITASK than endocardial myocytes (7.7±0.53pA) (t-test P<0.001; Fig. 1A⇓). To examine if ITASK was reflected by TASK-1 channel protein expression, we used immunocytochemistry with anti-TASK-1 antibody (Alomone, Israel) and fluorescence confocal microscopy. Performed on isolated myocytes, TASK-1 labelled protein (mean density per μm2) was 15.4±0.8 arb/μm2 within endocardial myocytes, but significantly less within epicardial myocytes at 8.4±0.3 arb/μm2 (t-test p<0.001; Fig. 1B⇓). Performed on sections of the left ventricular wall, line-scans showed a transmural decrease in TASK-1 labelled protein as shown in Figure 1C+D⇓. Thus, relative to the endocardial surface (100±4%) labelled TASK-1 protein was significantly reduced by 42±3% at the epicardial surface (n=49 sections; ANOVA p<0.001). Furthermore, Western blot of isolated single myocytes showed the endocardial myocytes contained 45% more TASK-1 protein than the epicardial myocytes (n=5 animals). Our novel findings validate our hypothesis: significantly more ITASK and TASK-1 protein is present in the endocardium that the epicardium.