Fig. 8: Chisel-1 selectively eliminates current through endogenous CaVβ1-associated HVACCs.
a Schematic of skeletal muscle Cav1.1 complex. b Images of isolated flexor digitorum brevis (FDB) fibers either untransfected (top) or transfected with Chisel-1-P2A-CFP (bottom). c Top, exemplar whole-cell currents from isolated FDB fibers expressing CFP (left) or Chisel-1 (right). Bottom, Population J-V curves from isolated FDB fibers expressing CFP (black squares; n = 13 over 3 independent experiments) or Chisel-1 (red squares; n = 13 over 3 independent experiments). d Top, exemplar gating currents from isolated FDB fibers expressing CFP (left) or Chisel-1 (right). Bottom, Population Q-V curves from isolated FDB fibers expressing CFP (black circles; n = 7 over 2 independent experiments) or Chisel-1 (red circles; n = 8 over 2 independent experiments). *P = 9.32 × 10−5 compared to CFP control, two-tailed unpaired t test. e Schematic of ventricular cardiomyocyte CaV1.2 complex. f Confocal images of cardiomyocytes expressing mCherry (top) or Chisel-1-P2A-mCherry (bottom). g Population J-V curves from isolated ventricular myocytes expressing mCherry (black triangles; n = 13 over 3 independent experiments) or Chisel-1 (red triangles; n = 11 over 3 independent experiments). h Top, exemplar whole-cell currents from ventricular myocytes expressing mCherry (left) or Chisel-1 (right) before (black) and after (cyan) application of 1 μM forskolin. Bottom, lack of effect of Chisel-1 on forskolin induced increase in ICa,L in ventricular myocytes (mCherry, n = 14; Chisel-1, n = 5). Data are means ± SEM. Source data are provided as a Source Data file.
