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. 2021 May 19;41(20):4378–4391. doi: 10.1523/JNEUROSCI.2537-20.2021

Figure 7.

Figure 7.

Ionic properties of MET channels from apical OHCs of Tmc1 p.D528N/D528N; Tmc2−/−. A, Three examples of single MET channel currents for Tmc1+/+; Tmc2−/−, ensemble average of 50 presentations (middle) and amplitude histogram (bottom) giving −7.1 pA at −84 mV. B, Examples of single MET channel currents for Tmc1 p.D528N/D528N; Tmc2−/−, ensemble average of 30 presentations (middle) and amplitude histogram (bottom) giving −4.6 pA at −84 mV, significantly smaller than control (p < 0.001). C, Determination of MET channel Ca2+ permeability in isotonic external Ca2+ and internal Cs+ (see Materials and Methods). During a sinusoidal bundle vibration (ΔX, ±200 nm), the membrane potential (Vm) was swept from −80 to +80 mV and the MET current reversed polarity at arrowed potential. Reversal potential in Tmc1 p.D528N/D528N; Tmc2−/− is ∼34 mV negative to Tmc1+/+; Tmc2−/− indicating much reduced Ca2+ permeability. D, Collected reversal potentials and relative permeability PCa/PCs in four cells each of Tmc1+/+, Tmc1 p.D528N/+ and Tmc1 p.D528N/D528N. All of which are significantly different (***) p < 0.001. Note the heterozygote reversal potential lies between wild type and homozygote. E, MET currents for bundle vibrations (ΔX, ±200 nm) in normal saline (black traces) and on adding DHS at 1 mm (top) and 10 mm (bottom) in Tmc1 p.D528N/D528N; Tmc2−/− (bottom). F, Mean ± SD (N = 5) of MET current block by DHS in Tmc1+/+ (N = 5) and Tmc1 p.D528N/D528N (N = 3). Hill plots give KI = 14 μm, Hill coefficient = 1 for control and 935 μm, Hill coefficient = 0.81 for mutant.