Figure 1. TMC1 mediates a background current in outer hair cells.

(A) Diagram of the recording configuration. The P6 outer hair cells (OHCs, mostly P6 apical-middle OHCs if not specified otherwise) in acutely dissociated cochlea were whole-cell voltage-clamped with Cs⁺ in the recording electrode and perfused with either 144 Na or 144 NMDG external solutions. 144 Na, regular recording solution; 144 NMDG, Na⁺ substituted with NMDG⁺. (B) Representative traces of membrane current (I_m) in OHCs from wild-type and Tmc1-knockout (Tmc1 KO) mice. The light gray and pink traces were recorded traces that were low-pass filtered to less noisy traces shown in black and red (similar filtering applied in the following figures). I_BG (background current) was calculated by subtraction of I_m in 144 Na (I_Na) and I_m in 144 NMDG (I_NMDG) to exclude technical leak. (C–E) Quantification of the I_Na (C), I_NMDG (D), and I_BG (E) measured from recordings similar to (B). Wild-type I_Na, –73 ± 6 pA, Tmc1-knockout I_Na, –21 ± 3 pA; wild-type I_NMDG, –7 ± 1 pA, Tmc1-knockout I_NMDG, –4 ± 1 pA; wild-type I_BG, –71 ± 5 pA, Tmc1-knockout I_BG, –18 ± 2 pA (F). Example of I_m in wild-type (black and gray) and Tmc1-knockout (red and pink) OHCs undergoing a series of membrane depolarization, with tissues bathed in 144 Na followed by 144 NMDG. (G–I) Composite data showing I-V curve (G), reversal potential (H), and I_BG (I) measured and calculated from recordings similar to (F). (G) I-V curve from recordings in 144 Na. (H) Mean reversal potentials calculated from I-V curve recorded in OHCs in 144 Na. (I) I_BG-V curve after subtracting I_NMDG. Only inward current was measured because NMDG was only applied extracellularly. The external solution contained 1.3 mM Ca²⁺. The holding potential was −70 mV. Data are presented as mean ± SEM. N values are shown in each panel. *p<0.05, **p<0.01, ***p<0.001, Student’s t-test.