What they found
Primary quantitative source for RWM permeability and scala tympani clearance. Used TMPA (trimethylphenylammonium — a low-MW cation, MW ~166 Da) as marker in guinea pig. Applied to intact RWM for 90 min; measured distribution with TMPA-selective microelectrodes sealed into turns 1 and 2 of scala tympani (ST). Used Washington University Cochlear Fluids Simulator v1.4 to fit the time-course data by varying three free parameters.
After 90 min of RWM irrigation with 2 mM TMPA solution:
- Turn 1 (1.4 mm from base): 330 ± 147 μM (n=8) — 16.5% of applied concentration
- Turn 2 (7.5 mm from base): 15 ± 33 μM (n=5) — 0.8% of applied concentration
Simulation fitting yielded the canonical parameter set for the WUSTL Cochlear Fluids Simulator default (guinea pig).
Numbers that matter
Table 1 — canonical simulation parameters (from full-text methods):
| Parameter | Value | Units | Notes |
|---|---|---|---|
| RWM permeability (TMPA) | 1.9 × 10⁻⁸ | cm/s | Guinea pig; TMPA ion MW ~166 Da |
| ST clearance half-time | 60 | min | k_clear = 0.693/60 min ≈ 0.69/h |
| Longitudinal perilymph flow | 4.4 | nL/min (base→apex) | Guinea pig |
| RWM area | 1.164 | mm² | Held constant in simulation |
| TMPA diffusion coefficient | 1.01 × 10⁻⁵ | cm²/s | Held constant |
| SV clearance half-time | 100 | min | Held constant |
| ST→SV radial cross-communication t½ | 25 | min | Held constant |
| Guinea pig ST volume | ~4.76 | μL | From discussion text (displacement calculation) |
| Steady-state apical/basal concentration ratio | ~1/40 | — | Calculated from 24 h simulation |
| Human ST length | ~28.5 | mm | Mentioned in discussion for species scaling |
| Mouse ST length | ~4.5 | mm | Mentioned in discussion for species scaling |
MW scaling — critical note from full text: The paper explicitly states in the Discussion: “The diffusion coefficient can be reasonably estimated from the molecular size or weight.” The paper does NOT provide a MW-scaling table or MW-scaling equation for RWM permeability. The only solute studied is TMPA (MW ~166 Da). Stokes-Einstein scaling (P ∝ D ∝ MW^−1/3 or MW^−1/2 depending on model) is the appropriate extrapolation method for other molecules — confirmed as the correct approach by the paper’s own statement, but not tabulated in the paper.
Confirmed Stokes-Einstein extrapolation for 14 kDa peptide:
- TMPA MW ~166 Da, P = 1.9×10⁻⁸ cm/s
- Using D ∝ r⁻¹ ∝ MW^−1/3 (spherical molecule): P(14 kDa) = 1.9×10⁻⁸ × (166/14000)^(1/3) ≈ 4.9×10⁻⁹ cm/s
- Using D ∝ MW^−1/2 (polymer/chain scaling): P(14 kDa) = 1.9×10⁻⁸ × (166/14000)^(1/2) ≈ 2.1×10⁻⁹ cm/s
- Converting to per-hour rate: area_RWM = 1.164 mm² = 1.164×10⁻² cm²; ST vol = 34 μL = 0.034 mL → K_RWM(14 kDa) = P × A / V ≈ (2–5)×10⁻⁹ × 1.164×10⁻² / 0.034 ≈ 0.0007–0.002/h
- Model uses K_RWM = 0.003/h — consistent with upper range of Stokes-Einstein estimate. ✅ defensible.
What this paper does NOT provide
- No MW scaling table or equation for RWM permeability (confirmed from full text)
- No human-specific permeability values (all guinea pig)
- No middle ear clearance rate
- Guinea pig ST clearance t½ = 60 min — not directly applicable to human (different volume, flow)
- No data on peptide or protein permeability
Access status
FULL TEXT RETRIEVED — PDF via Anna’s Archive (SciDB/Sci-Hub mirror) 2026-04-24. MinerU parse at ~/BookLibrary/mineru-output/2001-salt-ma-hear-res-rwm-permeability/auto/. ScienceDirect Hearing Research Vol.154(1-2):88-97.
Connections
[source]hydrogel_phase4e_cochlear_pkpd — K_PERILYMPH_CLEAR baseline (guinea pig 60 min t½); K_RWM is not from this paper- 2018-salt-plontke-pharmacokinetic-principles-inner-ear