A model of GABA transport by cortical synaptosomes from the Long-Evans rat.
The initial velocity of uptake of GABA by cortical synaptosomes from the Long-Evans rat has been measured as a function of both sodium and GABA concentration. These data were then fitted to the rate equation for each of several possible models, and the models giving least error were identified. Although one cannot unequivocally distinguish between two of the models on the basis of the goodness of fit, deductions based on the fits of subsets of the models point to one of the two models, The major predictions from this model are as follows: 1) Uptake of GABA is totally sodium-dependent. 2) Although plots of 1/v versus 1/[Na]2 are nonlinear, the coupling ratio for transport (Na/GABA) is 2. 3) For transport to take place, the order of combination with carrier must be Na, Na, GABA. 4) Maximal velocity will occur only at infinite Na and GABA concentrations. 5) There is a sigmoidal relationship between apparent maximal velocity (Va) and [Na]. 6) Kt, the [GABA] that gives a velocity equal to Va/2, rises and then falls as [Na] is increased from zero, passing through a maximum at 33.52 mM [Na]. 7) The relationship between initial velocity and [Na] is sigmoidal. 8) Jm, rate of uptake with infinite [Na], is hyperbolically related to [GABA]; Jm approaches Vmax as [GABA] becomes very large. 9) kappa Na, the [Na] giving a velocity equal to Jm/2, declines rapidly from 10(-7) M to 10(-5)M GABA, but is essentially constant at 10(-4)M above. 10) One GABA molecule is translocated per carrier molecule. The model is consistent with observations in the literature concerning the effects of sodium on the kinetics of transport.
D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D002352:Carrier Proteins / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism*; D003201:Computers; D007700:Kinetics; D008297:Male; D008433:Mathematics; D008954:Models, Biological; D051381:Rats; D012964:Sodium / Q000494:pharmacology; D013574:Synaptosomes / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D002352:Carrier Proteins; D005680:gamma-Aminobutyric Acid; D012964:Sodium