Extended Data Fig. 11: Membrane depolarization drives SCLC pathogenesis.
From: Neuronal activity-dependent mechanisms of small cell lung cancer pathogenesis
a, Representative calcium imaging of GCaMP6s-expressing 16T SCLC cells at baseline (left) and after application of 1 mM GABA. Scale bar = 100 μm. b, Quantification of GCaMP6s fluorescence in individual SCLC cells (from a) in response to administration of 1 mM GABA (n = 44 cells, p < 0.0001). c, As in b, but with administration of 1 mM glutamate (n = 19 cells, p < 0.0001). d, Quantification of the percent of cells exhibiting spontaneous calcium transients as depicted in Fig. 4i in SCLC tumors at baseline or with the addition of 0.5 µM TTX (p = 0.0002). e, Whole-cell patch-clamp voltage trace from ChR2-expressing SCLC cells (16T-ChR2) in response to blue light-induced depolarization. The lower panel represents the timing of blue light delivery. f, as in e, but demonstrating whole-cell patch-clamp current trace from ChR2-expressing SCLC cells (16T-ChR2). g, Quantification of proliferation index of 16T-ChR2 SCLC cells in mock-stimulated tumors or membrane depolarized tumors (n = 5 mock, n = 6 depolarized mice, p = 0.0460). Data are plotted as mean ± s.e.m. for d, g. Analysis with two-tailed paired t-test for b-c, two-tailed unpaired t-test for d, g. ****P < 0.0001, ***P < 0.001, **P < 0.01, *P < 0.05.
