Figure 8.

Direct delivery of exogenous FKBP12 protein into FKBP12^f/f/αMyHC-Cre⁺ ventricular cardiomyocytes replicates the effects of chronic FKBP12 overepxression on I_Na density and gating. A, Representative I_Na traces obtained from an FKBP12^f/f/αMyHC-Cre⁺ ventricular cardiomyocyte at 5 and 45 minutes into continuous dialysis with purified recombinant FKBP12 protein (1 μg/μl). B, I_Na remained unchanged in an FKBP12^f/f/αMyHC-Cre⁺ ventricular cardiomyocyte dialyzed with FKBP12-free pipette solution. C, Temporal changes in peak I_Na during continuous internal dialysis with FKBP12-containing and FKBP12-free, pipette solution, respectively. D, Normalized peak I_Na-V relationship at 5 and 45 minutes into FKBP12 dialysis. Internal perfusion of an FKBP12^f/f/αMyHC-Cre⁺ ventricular cardiomyocyte with FKBP12-free solution did not alter voltage-dependence of I_Na activation (not shown). E, Changes in voltage-dependence of I_Na activation and inactivation following FKBP12 application. F, The late I_Na/peak I_Na ratio is significantly increased following 45 minutes of FKBP12 dialysis. G, Representative action potential recordings over the course of FKBP12 dialysis. The arrow indicates the gradual prolongation of APD. H, Traces of dV/dt for the same action potentials shown in G. Traces were shifted along the time axis for display purposes.