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Figure 3 | Molecular Pain

Figure 3

From: Mutation I136V alters electrophysiological properties of the NaV1.7 channel in a family with onset of erythromelalgia in the second decade

Figure 3

I136V mutation alters recovery from fast-inactivation and increases currents elicited by slow ramp depolarizations. A, Cells were held at -100 mV, and fast-inactivation was initiated by a 20-ms depolarization to 0 mV, followed by a recovery period (2–300 ms) at a recovery potential, followed by a 10-ms test pulse to 0 mV to measure the available channels. Recovery rate were calculated by comparing the peak currents of test pulse to prepulse at 0 mV (20 ms) after various recovery durations (2–300 ms) at different recovery potentials (-100, -90, -80, and -70 mV), and plotted as a function of recovery potentials. Recovery time constants of NaV1.7R and I136V mutant channels were then estimated using single-exponential fits. At a recovery potential of -70 mV, I136V mutant channels (n = 11) recovered faster than wild type NaV1.7R channels (n = 12). B, Representative ramp currents from NaV1.7R (black) and I136V mutant (gray) channels. HEK293 cells were held at -100 mV and a depolarizing voltage ramp from -100 mV to +20 mV was applied at a rate of 0.2 mV/ms. The insert shows mean ramp currents of wild type NaV1.7R and I136V mutant channels. Currents were normalized to the maximal peak currents from step depolarizations in Figure 1B. I136V mutant channels were activated at more negative potentials and generated larger ramp currents than NaV1.7R channels (NaV1.7R: 0.23 ± 0.02, n = 19; I136V: 0.79 ± 0.04, n = 26, p < 0.05).

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