Mutations in S4 and the S4–S5 linker alter chemical sensitivity of TRPV1. A, sample recording of whole cell current responses to consecutive applications of capsaicin (1 μm) at −70 mV. B, averaged time constants obtained from monoexponential fit of the onset of first and second capsaicin response and deactivation times (T50) for all measurable mutants. The asterisks indicate significance level. C, whole cell currents in response to voltage protocol consisting of a 500-ms ramp from −70 mV to +100 mV applied every 2 s in the absence or presence of 10 μm capsaicin. D, averaged currents measured at 90 mV constructed from three to five independent recordings such as shown in C. The superimposed dotted line indicates wild type. Baseline was subtracted. E, 2-APB responses reduced by K571E mutation. Holding potential was −70 mV. F, mutation effects on 2-APB responses of TRPV1.