Effects of Intracellular and Extracellular Carbonic Anhydrase on the Influx of CO2 in a Xenopus Oocyte: Insights with a Mathematical Model

Abstract

Carbonic anhydrases (CAs) catalyze the interconversion of CO2 and HCO3, playing a key role in acid-base metabolism. Musa-Aziz et al (ASN-2005) showed that exposing oocytes to 1.5% CO2/10 mM HCO3 (pHo=7.5) causes intracellular pH (pHi) to fall and surface pH (pHS) to rise transiently and then decay, reflecting CO2 influx. Injecting CA II into oocytes accelerates the pHi decline and amplifies the pHS spike. Expressing CAIV on the extracellular surface causes an even faster pHi decline and higher pHS spike. Musa-Aziz et al propose that both CAII and CAIV enhance CO2 influx by maximizing transmembrane CO2 gradients. We explored the above results with a three-dimensional mathematical model of a Xenopus oocyte, where simultaneous diffusion and reaction processes (competing equilibria among HCO3 and non-HCO3 buffers) are modeled in both the extracellular unconvected solution (EUS) and intracellular fluid. We show how catalysis by CA and tortuosity factors, vitelline membrane, and solute mobilities influence the pHi and pHs profiles. The model predicts i) faster pHi decay when CAII activity is implemented and, in the presence of CAIV, ii) faster pHi decay when solute mobility in the EUS is reduced (mimicking the presence of the vitelline membrane and of the pHs electrode). Implementation of intracellular tortuosity factor explains the observed delay in the initial pHi decay.