STRC Research

calcium-oscillation

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Calcium oscillation — validated parameters

Source agent: Sonnet 4.6, 2026-04-23 (initial). Updated 2026-04-25 by Sonnet 4.6 — phantom resolution audit, 3 new ✅ rows, 4 phantom corrections. Consumer: h05 scripts (ca_oscillation_*.py, ca_osc_*.py).

MET channel — Ca²⁺ influx

ParameterValueSourceConditionsStatusUsed in
Single-channel conductance (apical OHC)150 pS2006-beurg-met-channel-conductance (Beurg J Neurosci 2006)Rat apical OHC, P5-7✅ primaryg_MET in rbm24 ODE
Single-channel conductance (basal OHC)210 pS2006-beurg-met-channel-conductanceRat basal OHC✅ primaryreference gradient
Ca²⁺ fraction of MET current0.152006-beurg-met-channel-conductance Table 2Physiological ionic✅ primaryf_Ca in rbm24 ODE
MET channels per OHC (apical, ~2/tip-link × 60–100 stereocilia)~120–200; model uses 1342014-fettiplace-kim-met-channel-review (Fettiplace & Kim Physiol Rev 2014, PMID 24987009)Review synthesis; 2 channels per tip link, 60–100 stereocilia/OHC✅ review synthesis; model value 134 is within rangen_channels in rbm24 ODE
Apical compartment volume~50 fL1998-lumpkin-hudspeth-stereocilia-calcium-regulation (Lumpkin & Hudspeth J Neurosci 1998, PMID 9698322)Bullfrog sacculus; derived from stereocilium geometry✅ paper note created 2026-04-25; species caveat (bullfrog)V_apex / V_APEX_L
Resting apical [Ca²⁺]20–310 nM; model 25–30 nM1998-lumpkin-hudspeth-stereocilia-calcium-regulationBullfrog saccular stereocilia, fluorescence imaging✅ paper note created 2026-04-25; resting ~60 nM at baseline, ~310 nM at max deflectionCa_rest, CA_REST_NM
Ca²⁺ buffer capacity (OHC apical compartment)100–1000×2005-hackney-calcium-buffering-proteins (Hackney et al. J Neurosci 2005, PMID 16120789) + 2010-beurg-calcium-balance-ohcRat OHC; oncomodulin 2-3 mM + calbindin 15-230 µM; functional equivalent ~1 mM BAPTA✅ paper notes created 2026-04-25; replaces ❌ “Müller et al. 2002” — no such paper found. Hackney 2005 is the correct primary source.buffer_ratio, BUFFER_CAP

Ca²⁺ clearance

ParameterValueSourceConditionsStatusUsed in
PMCA extrusion rate constant~30 /s (model estimate)1998-yamoah-pmca-stereocilia-extrusion (Yamoah et al. J Neurosci 1998, PMID 9425003) + 2010-beurg-calcium-balance-ohc (Beurg J Neurophysiol 2010, PMID 20427623)Bullfrog/rat OHC PMCA2; max extrusion 3.7 fmol/s; τ ~50 ms✅ paper notes created 2026-04-25; “Mammano 1999 Pflugers Arch” attribution was wrong — Mammano 1999 (PMID 10436049) is an IP3-gated Ca2+ store paper, not PMCA kinetics. Correct sources: Yamoah 1998 + Beurg 2010. k ~30 /s is a model-derived estimate, not directly reported.k_extrusion, K_EXTRUSION_S

AC1 (adenylyl cyclase type 1) kinetics

ParameterValueSourceConditionsStatusUsed in
Ca²⁺/CaM EC50 for AC1 activation100–500 nM2007-willoughby-cooper-adenylyl-cyclase-review (Willoughby & Cooper Physiol Rev 2007, PMID 17615394)Membrane preparations✅ review; model value 150 nM is within rangeK_CA_AC1_NM
Hill coefficient for Ca²⁺ activation1.5–2.52007-willoughby-cooper-adenylyl-cyclase-review—✅ model n=2 consistentN_CA_AC1
AC1 Vmax (cAMP synthesis)~2–5 µM cAMP/min in membrane prep2007-willoughby-cooper-adenylyl-cyclase-reviewReconstituted AC1⚠ model uses 2000 nM/s ≈ 120 µM/min — ~30-60× higher than membrane prep; cell-volume normalisation choice, not a measurementAC1_VMAX_NM_S
AC1 CaM binding mechanismCooperative; IQ-like domain; C-lobe driven2012-masada-ac1-ac8-calmodulin-kinetics (Masada Biochemistry 2012, PMID 22971080)Stopped-flow✅ mechanistic basis confirmed—

cAMP / PDE4 kinetics

ParameterValueSourceConditionsStatusUsed in
PDE4 Vmax for cAMP hydrolysis~10–20 µM/s (model)2003-houslay-adams-pde4-review (Houslay & Adams Biochem J 2003, PMID 12444918) — review, no primary VmaxNeuronal/epithelial estimates⚠ “Houslay 2010” phantom — no such paper exists. Houslay 2003 review is closest reference. Vmax is a model-fitted parameter with no primary hair-cell measurement.PDE4_VMAX_NM_S
PDE4 Km for cAMP~4 µM1997-owens-pde4a-kinetics (Owens et al. Biochem J 1997, PMID 9337850)Recombinant PDE4A in COS cells; Km = 4.8 µM full-length, 3.3 µM core✅ paper note created 2026-04-25; model value 4 µM is within the directly measured rangePDE4_KM_NM

PKA activation

ParameterValueSourceConditionsStatusUsed in
cAMP Kd for PKA holoenzyme (R2C2)~300 nM in-cell2007-willoughby-cooper-adenylyl-cyclase-review + Surdo et al. 2017 PMID 29074866In-cell FRET; in-vitro ~100 nM✅ 300 nM is the defensible in-cell value (Surdo 2017). Docstring previously cited “Zaccolo 2007” for 100 nM — that is the in-vitro value; mismatch now corrected in scripts.K_CAMP_PKA_NM
Hill coefficient for cAMP-PKA~2Standard regulatory subunit allostery—✅N_PKA

CREB phosphorylation / dephosphorylation

ParameterValueSourceConditionsStatusUsed in
PKA phosphorylation site on CREBSer1331989-gonzalez-montminy-creb-phosphorylation (Gonzalez & Montminy Cell 1989)HeLa/COS✅ canonicalmechanism
pCREB dephosphorylation t½5–10 min → k = 0.0012–0.0023/s1989-gonzalez-montminy-creb-phosphorylation and Montminy labNeuronal/HeLa✅ confirmed; model uses 0.005/s (2–4× faster — flagged as model choice in scripts; no OHC-specific source)K_CREB_DEPHOS_S
CRE half-saturation (CREB-P fraction)~0.2 fractional”Cha et al. 2010” — UNVERIFIED—⚠ PMID never confirmed; no “Cha 2010” CREB/CRE kinetics paper found in literature search. Retained as unsourced model parameter.K_CREB_CRE_HALF

STRC mRNA / protein turnover

ParameterValueSourceConditionsStatusUsed in
STRC mRNA t½NOT MEASURED — no primary literature”Sharma 2018” — PHANTOM (resolved 2026-04-25)—⚠ NOT MEASURED — value removed from model as primary measurement; retained only as unsourced calibration parameter. t½ ~2 h (pivot) vs ~30 min (rbm24) — both scripts now carry explicit # WARNING: no primary measurement comments.STRC_MRNA_DECAY_S, k_mRNA_deg
STRC protein t½NOT MEASURED — no primary literatureno source (PHANTOM resolved 2026-04-25)—⚠ NOT MEASURED — value removed from model as primary measurement; t½ 38 h (pivot) vs 30 days (rbm24) — 20× inconsistency remains as explicit unsourced flag in both scripts.K_PROT_DECAY_S, k_prot_deg
STRC protein copy number per OHCNOT MEASURED — no primary literature”Krey 2015” — PHANTOM (resolved 2026-04-25)—⚠ NOT MEASURED — 15,000/OHC is a model calibration set-point with no primary source. Krey 2015 (Wilmarth et al., Scientific Data, PMID 25977827) does not quantify STRC. No proteomics paper measures STRC copy number in mammalian OHC. Scripts carry explicit # WARNING comment.target_protein
RBM24 splicing effect on STRC (dPSI)0.5422026-04-17-sun-rbm24-strc-splicing (Sun PNAS 2026, PMID 41973913)Mouse cochlea✅ primary; paper note existsstrc_inclusion_min/max

CaMKII kinetics

ParameterValueSourceConditionsStatusUsed in
CaMKII Ca²⁺/CaM EC50~6 µM (full holoenzyme, short linker)2011-chao-camkii-holoenzyme-structure (Chao et al. Cell 2011, PMID 21884935)Human CaMKIIα holoenzyme; FRET assay✅ paper note created 2026-04-25. CRITICAL: PMID 21458670 (cited in scripts as “Chao 2011 Cell”) is actually Edlich et al. 2011 (Bcl-xL/Bax apoptosis paper, NO CaMKII content) — another phantom. Correct PMID is 21884935. Model uses Kd=1 µM, which is ~6× lower than measured EC50 for full holoenzyme activation.Kd_CaMKII
CaMKII autophosphorylation rate~0.5 /s (model; unmeasured)2011-chao-camkii-holoenzyme-structure — structural paper, k_auto not reported—⚠ k_auto is a model-fitted parameter. Chao 2011 does not report autophosphorylation rate constants. No primary measurement in OHC context.k_auto
Hill coefficient n (CaMKII activation)2.12011-chao-camkii-holoenzyme-structureShort-linker holoenzyme✅ from Chao 2011—

Calcineurin kinetics

ParameterValueSourceConditionsStatusUsed in
CaN Ca²⁺ EC50600–1300 nM1994-stemmer-klee-calcineurin-dual-calcium (Stemmer & Klee Biochemistry 1994, PMID 8204620)Purified CaN + CaM✅ primary; model 500 nM is slightly lowKd_CaN
CaN Hill coefficient2.8–31994-stemmer-klee-calcineurin-dual-calcium—✅ primary; model n=4 is slightly steepn_CaN_Hill
Frequency decoding conceptCaMKII accumulates high-freq; CaN activated by low-freq/sustained1998-dolmetsch-calcium-oscillations-gene-expression (Dolmetsch Nature 1998, PMID 9582075)T cells✅ conceptual basis confirmed; rate constants are fittedk_on/off_CaN

Phantom resolution summary (2026-04-25)

PhantomStatusResolution
”Sharma 2018” STRC mRNA t½RETRACTEDNo such paper. Value marked NOT MEASURED in table and scripts.
STRC protein t½ (no source)RETRACTEDNo primary literature. Value marked NOT MEASURED; cross-script inconsistency flagged.
”Krey 2015” STRC copy numberRETRACTEDKrey 2015 = Wilmarth et al. Scientific Data; does not quantify STRC. No paper does. Value marked NOT MEASURED.
”Chao 2011 Cell PMID 21458670” (CaMKII)RETRACTED + CORRECTEDPMID 21458670 = Edlich et al. 2011 Bcl-xL paper. Correct paper: Chao et al. 2011 Cell PMID 21884935. Paper note created.
”Mammano 1999 Pflugers Arch”CORRECTEDMammano 1999 = ATP/IP3 store paper (PMID 10436049); not PMCA kinetics. Correct sources: Yamoah 1998 (PMID 9425003) + Beurg 2010 (PMID 20427623). Paper notes created.
”Müller et al. 2002” buffer ratioCORRECTEDNo such paper found in any search. Correct source: Hackney et al. 2005 J Neurosci (PMID 16120789). Paper note created.
”Houslay 2010” PDE4 kineticsCORRECTEDNo such paper. Closest: Houslay & Adams 2003 (PMID 12444918, review). Primary Km: Owens et al. 1997 (PMID 9337850, 4.8 µM). Paper notes created.

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