Elimination of dantrolene inhibition by in vitro PKA phosphorylation and rapamycin is reversed by FKBP12.6. (A) RyR2 Po and mean open and closed dwell times (To and Tc) in the presence of 10 μM dantrolene relative to the mean of the bracketing intervals of dantrolene washout. RyR2s were subjected to in vitro dephosphorylation upon PKA phosphorylation prior to single channel recordings (PKA-PP1) or subsequently incubated with FKBP12.6 (FKBP12.6). An untreated sample is included for comparison. (B) As in A, except that RyR2 were subjected to rapamycin incubation instead of PKA and PP1. Error bars indicate mean ± SEM. P values denote a significant difference in relative value to 1, which in A are (left to right) 9 × 10−5, 0.2, 0.007, 0.72, 0.77, 0.48, 0.08, 0.92, and 0.074. In B these are 9 × 10−5, 0.08, 0.003, 0.72, 0.94. 0.021, 0.08, 0.05, and 0.043.
Figure 5.

Elimination of dantrolene inhibition by in vitro PKA phosphorylation and rapamycin is reversed by FKBP12.6. (A) RyR2 Po and mean open and closed dwell times (To and Tc) in the presence of 10 μM dantrolene relative to the mean of the bracketing intervals of dantrolene washout. RyR2s were subjected to in vitro dephosphorylation upon PKA phosphorylation prior to single channel recordings (PKA-PP1) or subsequently incubated with FKBP12.6 (FKBP12.6). An untreated sample is included for comparison. (B) As in A, except that RyR2 were subjected to rapamycin incubation instead of PKA and PP1. Error bars indicate mean ± SEM. P values denote a significant difference in relative value to 1, which in A are (left to right) 9 × 10−5, 0.2, 0.007, 0.72, 0.77, 0.48, 0.08, 0.92, and 0.074. In B these are 9 × 10−5, 0.08, 0.003, 0.72, 0.94. 0.021, 0.08, 0.05, and 0.043.

This Feature Is Available To Subscribers Only

or Create an Account

Close Modal
Close Modal