FIGURE 3.
Multimodal gating of TPC1. A, representative current recording of TPC1 expressed in HEK cells and obtained from the same bilayer (Vm,cyt = −40 mV) in the absence (control) and presence of 500 nm NAADP illustrating the presence of characteristic small (S) and large (L) open states. B, eight 400-ms fragments collected from the trace in panel A aligned by the time of the initial opening, illustrating appearance of the L conductance after opening of the S conductance. C, amplitude histograms were calculated from the 60-s long current recordings in A. Amplitude combinations of S and L conductances are indicated by arrows above the peaks. D, statistics of single channel openings collected from five different recordings of total duration of ∼14 min elucidating the prevalence of the S conductance and the coupling of S+L openings. E, open time probability histograms for single S conductance and coupled S and L openings analyzed in D. F, cumulative open time probability histogram yields median open times of 62 ms for single S openings, 420 ms for coupled S openings, and 20 ms for coupled L openings.