The effects of FKBP12.6 on the ability of FKBP12 to activate RyR2.

<p>(A) and (B) are typical examples of experiments where RyR2 Po was calculated in 10 s segments and plotted against time. (A) Pre-treatment with FKBP12.6 (200 nM). Control recordings were obtained in the presence of 10 µM cytosolic Ca²⁺ as the sole channel activator. As indicated by the bar, 200 nM FKBP12.6 was added to the cytosolic chamber. There was no obvious change in Po (perhaps a slight increase occurred but notice that Po, on average, remains well below 0.01) following the addition of 200 nM FKBP12.6. The subsequent sequential additions of increasing levels of FKBP12 did not elicit any obvious increases in Po. (B) Post FKBP12-treatment with FKBP12.6 (200 nM). Control recordings were obtained in the presence of 10 µM cytosolic Ca²⁺ as the sole channel activator. The bar indicates the time of incubation of the channel with 200 nM FKBP12 in the cytosolic chamber. The subsequent addition of 200 nM cytosolic FKBP12.6 (shown by the bar) did not reverse the activating effects of FKBP12. (C) Mean data illustrating that pre-treatment with 200 nM FKBP12.6 (as in the example shown in (A)), prevents channel activation by FKBP12 (1 µM). (D) Mean data showing that, on average, FKBP12.6 (200 nM) does not reverse the activation caused by FKBP12 on the timescale of a single-channel experiment, even when Po is monitored for 9 min after adding the FKBP12.6. Mean values ± SEM (n≥4; *<i>p</i><0.05) are shown.