Figure 1.
MEA recordings reveal differences in excitability between iPSC-SNs from subjects carrying the NaV1.7-S241T mutation and an unaffected control. A, Affected subjects P301 (mother) and P300 (son) carry the NaV1.7-S241T mutation, whereas P303 (unaffected father) carries only wild-type alleles. B, iPSC-SNs from P300, P301, and P303 express canonical sensory neuron markers and NaV1.7. Left, Peripherin (red), Brn3a (green), and Islet1 (gray). Figure 1-1, shows that the NaV1.7-S241T mutation is present in iPSC-SNs from P300 and P301, but not P303. Right, Peripherin (red), NaV1.7 (green), and Pan Neuronal Marker (gray). C, iPSC-SNs from all three subjects showed a neuronal morphology (microphotograph; scale bar, 20 μm), produced large sodium and potassium currents, and fired APs [examples from P301 (middle) and P300 (right)]. D, MEA recordings of AP firing of iPSC-SNs from P300, P301, and 303. Heatmaps show representative MEA recordings. The firing frequency of each active electrode is color coded: white/red, high firing frequency; blue/black, low firing frequency. Each circle represents an active electrode within an 8 × 8 electrode array. Top panels, Recordings from iPSC-SNs from P300 at 33°C, 37°C, and 40°C. Middle panels, Recordings from iPSC-SNs from P301 at 33°C, 37°C, and 40°C. Bottom panels, Recordings from iPSC-SNs from P303 at 33°C, 37°C, and 40°C. E, Representative MEA recordings showing neuronal firing at 33°C. F, Top, Average firing frequencies of neurons from P300, P301, and P303. Bottom, Average numbers of active electrodes for P300, P301, and P303 (average of three wells). *p < 0.05.