cAMP-activated chloride currents in human and mouse beta-cells. (A) Currents measured in a single human beta-cell after stimulation with voltage ramps in the absence (Ctrl, light gray) and presence of forskolin (FSK; gray), in the simultaneous presence of FSK and GlyH-101 (FSK and GlyH; black) and after wash-out of GlyH-101 to recover the FSK-activated current (WO: FSK; dark gray). Current ramps were applied before and every fourth minute after the application of FSK until a steady state was achieved. (B) Bar graph of the membrane conductance at negative voltages (left; n = 7 to 17, N = 3) and graph of calculated FSK-activated and CFTR-dependent current (right; Mean of n = 7 cells) from data in A. (C) Same as in A, but experiments where performed on mouse beta-cell. GlyH-101 (GlyH: black trace) and CFTRinh-172 (CFTRinh, black) was added to the left and right, as indicated. (D) As in B, but membrane conductance (left) was calculated from data in C (n = 10 to 17, N = 8). The mean result was combined for both CFTR-inhibitors (Inh). The calculated FSK-activated and CFTR-dependent current to the right is a mean from 10 cells. (E) As in A, but the effect of 4,4'-Diisothiocyano-2,2'-stilbenedisulfonic acid (DIDS) was investigated (n = 6, N = 2). Calculated FSK-activated, DIDS-sensitive and CFTR-currents shown to the right are mean of n = 5 cells. (F) Same as in E, but the membrane conductance (left) was calculated from measurements in mouse beta-cells (n = 9, N = 6) and the calculated current to the right is the mean from n = 8 cells. Data are presented as mean ± SEM. *P <0.05, ***P <0.005, ‡P <0.05, ‡‡‡P <0.005, †P <0.01 and ††P <0.01.
Edlund et al. BMC Medicine 2014 12:87 doi:10.1186/1741-7015-12-87