Fig. 3.

Trdn^−/− myocytes exhibit impaired Ca²⁺-dependent inactivation of L-type Ca²⁺ current. (A) (Top) Representative examples of L-type Ca²⁺ currents (I_Ca) recorded from Trdn^+/+ (+/+) and Trdn^−/− (−/−) myocytes in control conditions (CON) and in presence of 10 μM ryanodine (RY). (Bottom) Average current–voltage relationships. Myocyte size estimated by cell capacitance was not significantly different (+/+ 152 ± 4.3 pF; −/− 154 ± 3.7 pF; n = 20 each; P = 0.73). (B) Representative examples of superimposed normalized I_Ca records at 0 mV (Left) and averaged data (Right) in control conditions. Note that block of RyR2 channels with ryanodine abolished the differences in I_Ca inactivation. (C) I_Ca recordings in the presence of 1 μM ISO. −/− myocytes exhibit significantly larger I_Ca amplitudes. Note that ryanodine abolished the differences between +/+ and −/− myocytes. (D) I_Ca inactivation in ISO-stimulated myocytes. Although ryanodine reduced the differences between the 2 groups, I_Ca inactivation remained significantly slower in Trdn-/- myocytes even in the presence of RY. n = 7–10 myocytes from 3–4 different mice per genotype; ***, P < 0.001 vs. +/+.