Table 1.
Ionic properties of the MET channel in P5–P7 apical OHCs from mice with Tmc1 missense mutations, all of which cause deafness
| Apical OHC Tmc1; Tmc2-/- | D/R | Max MET current (nA) | Single channel conductance (pS) | PCa/Cs | POR 0.04 mm Ca | I0.04 Ca/I1.5 Ca | NMET |
|---|---|---|---|---|---|---|---|
| Tmc1+/+ | 1.18 ± 0.16 (N = 14) |
84.8 ± 3.1 (N = 5) |
4.25 ± 0.35 (N = 8) |
0.44 ± 0.06 (N = 8) |
1.54 ± 0.1 (N = 8) |
166 ± 23 (N = 5) |
|
| Tmc1 p.M412K/M412K(TMC1 p.M418K) | D | 1.14 ± 0.14 (N = 10) |
86.2 ± 8.2 (N = 5) |
1.50 ± 0.12*** (N = 10) |
0.19 ± 0.07*** (N = 7) |
1.49 ± 0.08 (N = 7) |
157 ± 20 (N = 5) |
| Tmc1p.T416K/T416K(TMC1 p.T422K) | D | 1.15 ± 0.10 (N = 18) |
87.2 ± 4.5 (N = 4) |
2.80 ± 0.5*** (N = 6) |
0.22 ± 0.06*** (N = 6) |
1.60 ± 0.20 (N = 6) |
157 ± 14 (N = 4) |
| Tmc1p.D528N/D528N | R | 0.55 ± 0.05*** (N = 11) |
53.3 ± 2.9 *** (N = 5) |
0.57 ± 0.04*** (N = 7) |
0.39 ± 0.01* (N = 4) |
1.48 ± 0.19 (N = 4) |
123 ± 12 (N = 5) |
| Tmc1p.W554L/W554L | R | 0.40 ± 0.10*** (N = 12) |
88.3 ± 4.0 (N = 4) |
3.59 ± 0.27** (N = 8) |
0.34 ± 0.02** (N = 6) |
1.49 ± 0.08 (N = 6) |
54 ± 13 (N = 4) |
| Tmc1p.D569N/D569N(TMC1 p.D572N) | D | 0.34 ± 0.13*** (N = 11) |
87.5 ± 4.5 (N = 5) |
1.25 ± 0.11*** (N = 10) |
0.24 ± 0.09*** (N = 7) |
1.51 ± 0.1 (N = 7) |
46 ± 18 (N = 5) |
D/R, mutations are semi-dominant (D) or recessive (R).
POR is resting open probability in 0.04 mm extracellular Ca2+; I increase is current ratio in 0.04 and 1.5 mm Ca2+; NMET number of MET channels is ratio of maximum to single-channel current, SD determined by max current. Each value mean ± SD. Mouse mutations (column 1) also show existing homologous human mutations. Human TMC1 numbering, with total 761 aa, differs from neonatal mouse with 757 aa. Significance tests between mutants and control (Tmc1+/+) t test:
*p < 0.05,
**p < 0.01,
***p < 0.001. Unstarred values were not significantly different from control Tmc1+/+, with p > 0.2.