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Simulations Obtained using a Model of Hemoglobin Desaturation‐Stimulated Gi Activation Accurately Predict Erythrocyte (RBC) ATP Release
Author(s) -
Goldman Daniel,
Sprague Randy S.,
Ellsworth Mary L.,
Ellis Christopher G.,
Stephenson Alan H.
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.814.18
Healthy human RBCs exposed to low oxygen tension release ATP via a pathway requiring activation of Gi and adenylyl cyclase, increases in cAMP, and activation of PKA and CFTR. We modeled this signaling pathway, incorporating time constants that are consistent with experimentally measured RBC ATP release. Here, we sought to validate this model over a range of measured RBC hemoglobin oxygen saturation values (98 to 22%). Our findings indicate that the behavior of the pathway model depends critically on the relationship between hemoglobin desaturation (tHb) and Gi activation. Measured ATP release, which is approximately quadratic in tHb, implies that Gi activation varies with a power of tHb on the order of 10. Using this relation, we can predict ATP release over the full range of tHb with a relative error of ~12%. This dynamic RBC ATP model complements our existing model of increases in plasma ATP that result from hemoglobin desaturation as blood traverses realistic three‐dimensional microvascular networks. The combined models lay the groundwork for future investigations of pathologies in which the stimulation of Gi in response to increased tHb is altered. [Supported by NIH grants HL‐089094 and HL‐089125 and a Presidential Grant from SLU].