Inhibition of Cardiac Kir Current (IK1) by Protein Kinase C Critically Depends on PKCβ and Kir2.2
Fig 2
Application of a small-molecule PKCβ inhibitor abolishes the inhibitory effect of thymeleatoxin on IK1 in rat ventricular cardiomyocytes.
Whole-cell patch-clamp experiments with isolated rat ventricular cardiomyocytes were performed using thymeleatoxin (TMTX 100 nmol/l) as PKC activator. A typical experiment is displayed in panels (A–C). Panel (D) shows the time course of effect. BaCl2, applied at the end of the observation period induced only a slight further current inhibition, i.e. about 84% of barium-sensitive currents had been inhibited by TMTX before. Currents remained nearly unaltered when the PKCβ inhibitor (3 μmol/l) was co-applied with TMTX (E). Subsequent application of BaCl2 to the bath at the end of the observation period lead to a fast block of inward currents. (F) Summary data of all experiments in rat ventricular cardiomyocytes. Protocol: holding potential -80 mV; test pulses from -130 mV to -80 mV in 10 mV-increments (200 ms). * indicates statistical significance.