Figure 2. Inhibition of CFTR increases [Ca²⁺]_i via L-type Ca²⁺ channels.

A, quiescent WT ventricular myocytes were loaded with fura-2 to monitor changes in [Ca²⁺]_i. Following a 3 min baseline period, either CFTR_inh-172 (20 μm, n= 32) or DMSO (n= 19) was added, and subsequent effects were measured for 20 min. B, representative trace (n= 12) of spontaneously beating cardiomyocyte that was loaded with fura-2 to measure Ca²⁺ transients prior to and after CFTR_inh-172 (20 μm) addition. Separate experiments with DMSO showed no change in diastolic or systolic Ca²⁺ (data not shown; n= 4). C, quiescent WT cardiomyocytes were bathed in Ca²⁺-free solution (n= 25), pretreated with ryanodine (10 μm) and thapsigargin (1 μm; n= 26), KB-R7943 (10 μm; n= 23), nifedipine (10 μm; n= 26) or KB-R7943 and nifedipine (n= 23) for 30 min prior to [Ca²⁺]_i measurements. Additionally, in myocytes from CFTR KO mice, fura-2 fluorescence was monitored upon CFTR_inh-172 (20 μm; n= 23) or DMSO (n= 24) addition. ***P < 0.001 vs. CFTR_inh-172 by Student's unpaired t test; NS, not significant.