Mathematical model of the spatio-temporal dynamics of second messengers in visual transduction.
A model describing the role of transversal and longitudinal diffusion of cGMP and Ca(2+) in signaling in the rod outer segment of vertebrates is developed. Utilizing a novel notion of surface-volume reaction and the mathematical theories of homogenization and concentrated capacity, the diffusion of cGMP and Ca(2+) in the inter-disc spaces is shown to be reducible to a one-parameter family of diffusion processes taking place on a single rod cross section; whereas the diffusion in the outer shell is shown to be reducible to a diffusion on a cylindrical surface. Moreover, the exterior flux of the former serves as a source term for the latter, alleviating the assumption of a well-stirred cytosol. A previous model of visual transduction that assumes a well-stirred rod outer segment cytosol (and thus contains no spatial information) can be recovered from this model by imposing a "bulk" assumption. The model shows that upon activation of a single rhodopsin, cGMP changes are local, and exhibit both a longitudinal and a transversal component. Consequently, membrane current is also highly localized. The spatial spread of the single photon response along the longitudinal axis of the outer segment is predicted to be 3-5 microm, consistent with experimental data. This approach represents a tool to analyze point-wise signaling dynamics without requiring averaging over the entire cell by global Michaelis-Menten kinetics.
Andreucci
D
D
Dipartimento di Metodi e Modelli Matematici, Università di Roma La Sapienza, 00161 Rome, Italy.
Bisegna
P
P
Caruso
G
G
Hamm
H E
HE
DiBenedetto
E
E
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D003198:Computer Simulation; D006152:Cyclic GMP / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D004058:Diffusion; D007700:Kinetics; D008027:Light; D008962:Models, Theoretical; D017785:Photons; D010786:Photoreceptor Cells / Q000502:physiology; D012374:Rod Cell Outer Segment / Q000502:physiology; D015398:Signal Transduction; D013997:Time Factors; D014785:Vision, Ocular / Q000502:physiology*
D006152:Cyclic GMP; D002118:Calcium