Immunogold EM quantification of calcium-buffering proteins in rat cochlear hair cells across development (P7, P16, P26). Primary source for the buffer_ratio parameter in h05 ODE models. The “Müller et al. 2002” attribution for buffer ratio 200-1000× in the h05 literature table is not found in the literature — the Hackney 2005 paper is the correct primary source. No Müller 2002 calcium buffer paper has been identified in any search.
Key finding
Mature rat OHC (P26) contains oncomodulin (parvalbumin-β) at 2-3 mM and calbindin-D28k at 15-230 µM (apex to base), totaling ~5-6 mM Ca2+-binding sites. OHC buffer capacity is ~110× that of IHC. Both proteins are partially excluded from stereocilia bundles, permitting faster unbuffered Ca2+ regulation at the MET channels. This supports a high cytoplasmic buffer ratio while the apical compartment (stereocilia) has lower buffering — relevant to h05 model parameter split between cytoplasm and stereocilia.
Numbers that matter
| Parameter | Value | Units | Conditions | Notes |
|---|---|---|---|---|
| Oncomodulin (parvalbumin-β) in OHC | 1954–2892 | µM | Rat P26, apex to base | Expressed as immunogold-calibrated concentration |
| Calbindin-D28k in OHC | 15–230 | µM | Rat P26, basal to apical | Large tonotopic gradient |
| Total Ca2+-binding sites in OHC | ~5–6 | mM | P26, mature OHC | Equivalent Ca2+-binding capacity |
| OHC/IHC buffer ratio | ~110 | × | P26 | OHC has ~110× more proteinaceous Ca2+ buffer |
| Stereocilia vs cytoplasm | 3.5–5× lower | — | Both parvalbumin-β and calbindin | Partially excluded from stereocilia |
| Buffer ratio (κ, derived) | ~100–1000 | Ca2+-bound/Ca2+-free | Model-dependent | Hackney 2005 gives binding sites but not explicit κ; model value 1000 is upper end |
Buffer ratio derivation: With 5 mM binding sites and Kd ~300 nM for calbindin, κ = [Ca-buffer]/[Ca-free] ≈ 5e-3 / (Kd + [Ca]×…). At [Ca] = 30 nM, most sites free; κ is high. The model range 100–1000× is consistent with Hackney 2005 if binding kinetics of oncomodulin (Kd ~1 µM) and calbindin (Kd ~300 nM) are applied.
Limitations
- Immunogold EM gives relative, not absolute concentrations; calibration with known standards introduces uncertainty of ~20-30%.
- Partial exclusion from stereocilia means OHC body values overestimate stereocilia buffer.
- No “Müller 2002” paper found in any literature search — that attribution in h05 literature table is unverified phantom.
Connections
[source]calcium-oscillation — primary source for buffer_ratio and oncomodulin context[see-also]2010-beurg-calcium-balance-ohc — complements with functional buffer equivalence (1 mM BAPTA)[applies]STRC Calcium Oscillation Acoustic Therapy