What they found
In Jurkat T cells, Ca²⁺ oscillations (rather than sustained Ca²⁺ elevations) activate NF-κB, NF-AT, and Oct/OAP transcription factors with high efficiency and specificity. The key finding: different transcription factors have different threshold frequencies — NF-AT is activated at low frequencies; NF-κB requires higher frequency. CaMKII autophosphorylation accumulates preferentially with high-frequency oscillations; calcineurin (which dephosphorylates and activates NF-AT) is activated by lower-frequency sustained signals. This establishes the concept of frequency decoding of Ca²⁺ signals.
Numbers that matter
- Optimal oscillation frequency for NF-κB: ~0.2–0.5 Hz
- Calcineurin (NF-AT pathway) activated by low-frequency/sustained Ca²⁺: EC50 ~ 200–500 nM
- CaMKII switches to sustained activity at higher frequencies due to autophosphorylation memory
- Rate constants
k_on_CaN = 0.3/sandk_off_CaN = 0.05/sin the h05 model are not directly from this paper — they are fitted values consistent with the conceptual framework
Fit to h05
The RBM24 ODE Phase 1 model is built on the Dolmetsch frequency-decoding concept. Dolmetsch 1998 confirms the biological plausibility of the CaMKII:CaN ratio as a Ca²⁺ frequency readout. However, the specific rate constants used in the model are estimates, not direct measurements from this paper. The paper does not study cochlear hair cells.
Connections
- STRC Calcium Oscillation Acoustic Therapy — conceptual basis for RBM24 ODE frequency decoder
[see-also]1994-stemmer-klee-calcineurin-dual-calcium — calcineurin kinetics[part-of]calcium-oscillation (literature-params topic)