Figure 6
From: Calcineurin Controls Voltage-Dependent-Inactivation (VDI) of the Normal and Timothy Cardiac Channels
FK-506 restores Timothy channel inactivation.
ICa was elicited in oocytes expressing α11.2G406R/α2δ1/β2b (Cav1.2G406R) from a holding potential of -80 mV to various test potentials in 5 mV increments, in response to 1200 ms pulse (a) representative ICa traces elicited in the absence and in the presence of 0.1, 1.0 and 10 µM FK-506 (b) Current–voltage relationship of G406R in the absence and in the presence of FK-506, at the indicated concentrations (c) Peak current amplitudes normalized to maximum current (taken from (b)) shown as I/Imax ratios of inward currents of G406R channel in the presence and in the absence of FK-506 are plotted against test potentials and displayed with a Boltzmann fit (mean ± S.E.M; n = 10–12; more details in supporting online text) (d) The time constant of activation (τact, mean±S.E.M., n = 10), fitted by a single exponent (e) Steady-state inactivation recorded in stimulated wt (left) and G406R channel (right) with or without 1 µM CsA, according to a multistep protocol of VDI measurements (Fig. 1C inset). Normalized currents were fitted to the Boltzmann equation (Methods).
