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	Fig 1. Effects of different protein kinase C activators on Kir2.1 and Kir2.2 currents indicate a pronounced inhibitory regulation of Kir2.2 by conventional PKC isoforms with a predominant role of PKCβ.Representative recordings of Kir2.1 currents before and after superfusion with PMA (1 μmol/l) for 30 minutes (A-B). Corresponding IV-curves (C). Typical recording of Kir2.2 currents under control conditions (D), after superfusion with PMA (1 μmol/l) for 30 minutes (E) and corresponding IV-curves (F). (G) Summary data of the experiments with different PKC activators is shown for Kir2.1. (H) Summary data of the experiments with different PKC activators and co-applied PKCβ inhibitor is shown for Kir2.2. * indicates statistically significant difference to control experiments. These data point to a pronounced inhibitory regulation of Kir2.2 currents by PKC that predominantly depends on conventional PKC isoforms with a crucial role of PKCβ. In contrast, the moderate inhibition of Kir2.1 channels by PMA is likely to be independent of PKC signalling pathways. Protocol: holding potential -80 mV; test pulses from -120 mV to +40 mV in 10 mV-increments (400 ms).
	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.
	Fig 3. In homozygous PKCβ-knockout mice the ventricular IK1 is not inhibited after PKC activation with thymeleatoxin.Isolated ventricular cardiomyocytes from wild type (A-C) and PKCβ-knockout mice (D-F) were examined using the whole-cell patch-clamp configuration. Thymeleatoxin (TMTX; 100 nmol/l) was used for PKC activation. The same voltage protocol as in the experiments with rat ventricular cardiomyocytes was used. (G-H) Summary data from the experiments using cardiomyocytes from wild type and PKCβ-knockout mice. BaCl2 induced a rapid inhibition of inward currents in PKCβ-knockout mice but not in wild type mice, pointing to a nearly absent PKC regulation of IK1 in PKCβ-knockout mice. * indicates statistical significance.
	Fig 4. Heteromeric Kir2.1/Kir2.2 channels are inhibited by protein kinase C.Heteromeric Kir2.1/Kir2.2 channels were expressed as concatemers according to Preisig-Müller et al. (2002) [3]. (A-C) A representative experiment and corresponding IV-curves. (D) Summary data of relative currents upon activation of PKC by thymeleatoxin (TMTX; 100 nmol/l) compared to measurements of Kir2.1/Kir2.2 heteromeric channels under control conditions. * indicates statistical significance.
	Fig 5. The functional PKC consensus sites S64 and T353 are lacking in Kir2.1 channels.(A) Alignment of the amino acid sequence of Kir2.1 and Kir2.2. Interestingly, in Kir2.1 channels, the PKC consensus sites S64 and T353 which have been shown to be functionally relevant are lacking. (B) Schematic picture of a Kir2.2 channel subunit with the suggested locations of the PKC phosphorylation sites.

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