Calcium oscillation — validated parameters

Source agent: Sonnet 4.6, 2026-04-23. Consumer: h05 scripts (ca_oscillation_*.py, ca_osc_*.py).

MET channel — Ca²⁺ influx

Parameter	Value	Source	Conditions	Status	Used in
Single-channel conductance (apical OHC)	150 pS	2006-beurg-met-channel-conductance (Beurg J Neurosci 2006)	Rat apical OHC, P5-7	✅ primary	`g_MET` in rbm24 ODE
Single-channel conductance (basal OHC)	210 pS	2006-beurg-met-channel-conductance	Rat basal OHC	✅ primary	reference gradient
Ca²⁺ fraction of MET current	0.15	2006-beurg-met-channel-conductance Table 2	Physiological ionic	✅ primary	`f_Ca` in rbm24 ODE
MET channels per OHC (apical, ~2/stereocilium × 67 stereocilia)	~134	2014-fettiplace-kim-met-channel-review (Fettiplace & Kim Physiol Rev 2014)	Estimated; variable by CF	⚠ estimate (review synthesis)	`n_channels` in rbm24 ODE
Apical compartment volume	~50 fL	Lumpkin & Hudspeth 1998 J Neurosci — NEEDS NOTE	Bullfrog sacculus	⚠ needs paper note	`V_apex` / `V_APEX_L`
Resting apical [Ca²⁺]	20–40 nM	Lumpkin & Hudspeth 1998 — NEEDS NOTE	Stereocilia, fluorescence	⚠ needs paper note	`Ca_rest`, `CA_REST_NM`
Ca²⁺ buffer capacity (OHC apical compartment)	100–1000×	Müller et al. 2002, oncomodulin literature	OHC calbindin + oncomodulin	❌ no single primary source	`buffer_ratio`, `BUFFER_CAP`

Parameter	Value	Source	Conditions	Status	Used in
PMCA extrusion rate constant	~30 /s	Mammano 1999 (Pflugers Arch?) — NEEDS PMID	OHC PMCA2	⚠ needs PMID confirmation	`k_extrusion`, `K_EXTRUSION_S`

Parameter	Value	Source	Conditions	Status	Used in
Ca²⁺/CaM EC50 for AC1 activation	100–500 nM	2007-willoughby-cooper-adenylyl-cyclase-review (Willoughby & Cooper Physiol Rev 2007)	Membrane preparations	✅ review; model value 150 nM is within range	`K_CA_AC1_NM`
Hill coefficient for Ca²⁺ activation	1.5–2.5	2007-willoughby-cooper-adenylyl-cyclase-review	—	✅ model n=2 consistent	`N_CA_AC1`
AC1 Vmax (cAMP synthesis)	~2–5 µM cAMP/min in membrane prep	2007-willoughby-cooper-adenylyl-cyclase-review	Reconstituted AC1	⚠ model uses 2000 nM/s ≈ 120 µM/min — likely overestimate unless normalized to cell volume	`AC1_VMAX_NM_S`
AC1 CaM binding mechanism	Cooperative; IQ-like domain; C-lobe driven	2012-masada-ac1-ac8-calmodulin-kinetics (Masada Biochemistry 2012)	Stopped-flow	✅ mechanistic basis confirmed	—

Parameter	Value	Source	Conditions	Status	Used in
PDE4 Vmax for cAMP hydrolysis	~10–20 µM/s	Houslay lab reviews (no single 2010 PMID confirmed)	Epithelial / neuronal	⚠ attributed to “Houslay 2010” — NEEDS SPECIFIC PMID	`PDE4_VMAX_NM_S`
PDE4 Km for cAMP	~4 µM	Houslay lab — same provenance issue	—	⚠ NEEDS SPECIFIC PMID	`PDE4_KM_NM`

Parameter	Value	Source	Conditions	Status	Used in
cAMP Kd for PKA holoenzyme (R2C2)	~100–300 nM	Zaccolo & Pozzan 2002 + in-cell studies	In-cell FRET measurements	⚠ model uses 300 nM; docstring cites “Zaccolo 2007” for 100 nM — value-citation mismatch. In-cell PKA activation requires higher [cAMP] than in vitro (PMID 29074866: ~300 nM in cell vs ~100 nM in vitro). 300 nM is the more defensible value.	`K_CAMP_PKA_NM`
Hill coefficient for cAMP-PKA	~2	Standard regulatory subunit allostery	—	✅	`N_PKA`

Parameter	Value	Source	Conditions	Status	Used in
PKA phosphorylation site on CREB	Ser133	1989-gonzalez-montminy-creb-phosphorylation (Gonzalez & Montminy Cell 1989)	HeLa/COS	✅ canonical	mechanism
pCREB dephosphorylation t½	5–10 min → k = 0.0012–0.0023/s	1989-gonzalez-montminy-creb-phosphorylation and later Montminy lab	Neuronal/HeLa	✅ confirmed; model uses 0.005/s (2–4× faster — value-citation discrepancy, flag)	`K_CREB_DEPHOS_S`
CRE half-saturation (CREB-P fraction)	~0.2 fractional	”Cha et al. 2010” — NEEDS PMID	—	⚠ citation unverified	`K_CREB_CRE_HALF`

Parameter	Value	Source	Conditions	Status	Used in
STRC mRNA t½	unknown	”Sharma 2018” — PHANTOM CITATION	—	🚨 No such paper found. t½ ~2 h in pivot, ~30 min in rbm24 — inconsistent between scripts. NEEDS REAL SOURCE.	`STRC_MRNA_DECAY_S`, `k_mRNA_deg`
STRC protein t½	unknown	no source	—	❌ t½ 38 h (pivot) vs 30 days (rbm24) — 3-order-of-magnitude inconsistency between scripts. NEEDS RESOLUTION.	`K_PROT_DECAY_S`, `k_prot_deg`
STRC protein copy number per OHC	unknown	”Krey 2015” — PHANTOM	—	🚨 Krey 2015 (Wilmarth et al., Scientific Data) does not quantify STRC. No primary source for 15,000 molecules/OHC exists.	`target_protein`
RBM24 splicing effect on STRC (dPSI)	0.542	2026-04-17-sun-rbm24-strc-splicing (Sun PNAS 2026, PMID 41973913)	Mouse cochlea	✅ primary; paper note exists	`strc_inclusion_min/max`

Parameter	Value	Source	Conditions	Status	Used in
CaMKII Ca²⁺/CaM Kd	~0.5–1 µM	”Chao et al. 2010” — likely Chao 2011 Cell (PMID 21458670)	Structural	⚠ year probably wrong; value plausible	`Kd_CaMKII`
CaMKII autophosphorylation rate	~0.5 /s at saturation	”Chao et al. 2010”	—	⚠ same citation issue; value order-of-magnitude plausible	`k_auto`

Parameter	Value	Source	Conditions	Status	Used in
CaN Ca²⁺ EC50	600–1300 nM	1994-stemmer-klee-calcineurin-dual-calcium (Stemmer & Klee Biochemistry 1994, PMID 8204620)	Purified CaN + CaM	✅ primary; model 500 nM is slightly low	`Kd_CaN`
CaN Hill coefficient	2.8–3	1994-stemmer-klee-calcineurin-dual-calcium	—	✅ primary; model n=4 is slightly steep	`n_CaN_Hill`
Frequency decoding concept	CaMKII accumulates high-freq; CaN activated by low-freq/sustained	1998-dolmetsch-calcium-oscillations-gene-expression (Dolmetsch Nature 1998, PMID 9582075)	T cells	✅ conceptual basis confirmed; rate constants are fitted, not measured in this paper	`k_on/off_CaN`

“Wu 2011” (AC1 kinetics) — phantom citation. Replace with Masada 2012 (PMID 22971080) + Willoughby & Cooper 2007 (PMID 17615394). The K_Ca = 150 nM and AC1 Vmax values are supported in range but not as exact numbers from a 2011 Wu paper.
“Sharma 2018” (STRC mRNA t½) — phantom citation. No such paper exists. The mRNA t½ is a free parameter. Flag as estimated.
“Krey 2015” (target_protein = 15000) — phantom on two levels: (a) Krey 2015 (Wilmarth Scientific Data) does not quantify STRC in mammalian OHCs; (b) no paper anywhere quantifies STRC copy number per OHC. Flag as estimated.
STRC protein t½ inconsistency — pivot uses 38 h; rbm24 uses 30 days. These disagree by 20×. Must be reconciled before cross-script comparison of protein output is meaningful.
STRC mRNA t½ inconsistency — pivot uses ~2 h; rbm24 uses ~30 min. Disagree by 4×.
K_CREB_DEPHOS_S value-citation mismatch — Gonzalez & Montminy 1989 implies k = 0.0012–0.0023/s but model uses 0.005/s (2–4× faster). The 1.82× upregulation result depends on how long pCREB persists at high SPL; a 4× slower dephos rate would push fold-change higher, which would strengthen the hypothesis.
“Zaccolo 2007” value-citation mismatch — cites 100 nM but implements 300 nM. The 300 nM value is more defensible for in-cell PKA activation; the citation is wrong. Use PMID 29074866 (Surdo et al. 2017) for the in-cell 300 nM justification.

[part-of] _hub (literature-params)
[see-also] stereocilia-mechanics — bundle stiffness parameters shared with h09/h26
[applies] STRC Calcium Oscillation Acoustic Therapy — h05 main hypothesis
[applies] STRC AC1-CREB Alternative Hypothesis