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. 2014 Jul 15;5:4420. doi: 10.1038/ncomms5420

Figure 3. Involvement of CFTR-mediated Cl− efflux in glucose-induced electric spikes and calcium oscillations in β-cells.

Figure 3

(a) Glucose (10 mM) elicited a slow membrane depolarization superimposed with bursts of action potentials (spikes) in isolated mouse islet β-cells (enlarged in I), which could be abolished by CFTRinh-172 (10 μM) (enlarged in II). n=4. (b) Islet β-cells from DF508 mice required a significantly longer time to reach the threshold for spike generation and had a smaller magnitude and frequency of glucose (10 mM)-induced spikes than that from the wild types. Number of measurements is shown in each column *P<0.05, ***P<0.001, t-test. (c) When the membrane potential was clamped to −65 mV similar to that observed in wild-type, DF508 β-cells (lower panel) still exhibited a reduced magnitude of the glucose-induced spike than that from wild type (upper panel). Number of measurements is shown in each column. *P<0.05, t-test. (d) Upper panel: when the membrane potential was clamped to depolarization voltage (−40 mV), electric spikes generated in wild-type β-cells exhibited higher magnitude and frequency than that in DF508. Lower panel: when the membrane potential was elevated to a depolarized level, −50 mV, CFTRinh-172 (10 μM) decreased the spike frequency and amplitude in RINm5F cells. Number of measurements is shown in each column. *P<0.05, ***P<0.001, t-test. [Cl−]o=142 mM; [Cl−]i=150 mM and ECl=1.41 mV (a–d). (e) Intracellular chloride concentration-dependent action potential in RINm5F cells. [Cl−]o=142 mM; ECl=1.4, −16.5 and −∞ with [Cl−]i at 150, 75 and 0 mM, respectively. n=4. **P<0.01; ***P<0.001, one-way analysis of variance (ANOVA). (f) When Cl− was removed from the pipette solution, the glucose-induced electric spikes were almost completely abolished in RINm5F cells. (g) Effect of CFTRinh-172 (10 μM) and glyH-101 (10 μM) on glucose (10 mM)-induced intracellular Ca2+ and oscillations measured by Fura-2 in RINm5F cells. Number of measurements is shown in each column. ***P<0.001, one-way ANOVA. (h) Glucose (10 mM)-induced Ca2+ increase and oscillations in β cells isolated from the wild-type and DF508 mice with or without CFTRinh-172 (10 μM). Number of measurements is shown in each column. ***P<0.001, one-way ANOVA. Data are shown as mean±s.e.m.