What they found
Comprehensive review of all mammalian adenylyl cyclase isoforms, with emphasis on Ca²⁺-regulated isoforms (AC1, AC3, AC8 as Ca²⁺/CaM-stimulated; AC5, AC6 as Ca²⁺-inhibited). For AC1 specifically: Ca²⁺/CaM stimulation is cooperative, EC50 for Ca²⁺ is in the 100–500 nM range (depending on assay conditions), and Vmax in reconstituted systems is in the µM/min range. Review synthesizes data from multiple labs on cAMP microdomain signaling and the spatial organization of AC isoforms with PKA scaffolds (AKAPs).
Numbers that matter
- AC1 EC50 for Ca²⁺ (via CaM): ~100–500 nM (assay-dependent; K_Ca = 150 nM used in h05 model is within this range)
- AC1 Vmax: ~2–5 µM cAMP/min in membrane preparations; Vmax = 2000 nM/s ≈ 120 µM/min is likely an overestimate unless at saturation in a concentrated cell compartment
- AC1 Hill coefficient for Ca²⁺ activation: 1.5–2.5 (n=2 in model is consistent)
- AC1 mRNA/protein expression: highest in neurons, cochlea, olfactory bulb; expressed in cochlear IHC and OHC (cited separately as Visel 1997/Vorobiova 1997 series)
- This is the canonical reference that should replace the phantom “Wu 2011” citation
Fit to h05
Willoughby & Cooper 2007 is the correct source for the AC1 kinetic rationale in the h05 pivot model. The model’s K_CA_AC1_NM = 150 nM falls within the reported EC50 range; AC1_VMAX_NM_S = 2000 nM/s needs to be checked against cell-level measurements (membrane prep values converted to cytoplasmic concentrations depend on AC1 copy number, which is not specified in the model).
Connections
- STRC Calcium Oscillation Acoustic Therapy — replaces phantom “Wu 2011”
[see-also]2012-masada-ac1-ac8-calmodulin-kinetics — mechanistic follow-up[part-of]calcium-oscillation (literature-params topic)