PubMed · 3949404
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A W Grogono. 1986. Acid-base balance.. https://doi.org/10.1097/00004311-198602410-00003
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Previous studies have shown that chemical regulation of connexin43 (Cx43) depends on the presence of the carboxyl terminal (CT) domain. A particle-receptor (or "ball-and-chain") model has been proposed to explain the mechanism of gating. We tested whether the CT region behaved as a functional domain for other members of the connexin family. The pH sensitivity of wild-type and Ct-truncated connexins was quantified by use of electrophysiological and optical techniques and the Xenopus oocyte system. The CT domain of Cx45 had no role in pH regulation, although a partial role was shown for Cx37 and Cx50. A prominent effect was observed for Cx40 and Cx43. In addition, we found that the CT domain of Cx40 that was expressed as a separate fragment rescued the pH sensitivity of the truncated Cx40 (Cx40tr), which was in agreement with a particle-receptor model. Because Cx40 and Cx43 often colocalize and possibly heteromerize, we tested the pH sensitivity of Cx40tr when coexpressed with the CT domain of Cx43 (hetero-domain interactions). We found that the CT domain of Cx43 enhanced the pH sensitivity of Cx40tr; similarly, the CT domain of Cx40 restored the pH sensitivity of the truncated Cx43. In addition, the CT domain of Cx43 granted insulin sensitivity to the otherwise insulin-insensitive Cx26 or Cx32 channels. These data show that the particle-receptor model is preserved in Cx40 and the regulatory domain of one connexin can specifically interact with a channel formed by another connexin. Hetero-domain interactions could be critical for the regulation of heteromeric channels.
Mitochondrial cytochromes c from spinach, cucumber, and sweet potato have been investigated through direct electrochemical measurements and electronic and 1H NMR spectroscopies, under conditions of varying temperature and pH. The solution behaviors of these plant cytochromes closely resemble, but do not fully reproduce, those of homologous eukaryotic species. The reduction potentials (E0') at pH 7 and 25 degrees C are +0.268 V (spinach), +0.271 V (cucumber), and +0.274 V (sweet potato) vs SHE. Three acid-base equilibria have been determined for the oxidized proteins with apparent pKa values of 2.5, 4.8, and 8.3-8.9, which are related to disruption of axial heme ligation, deprotonation of the solvent-exposed heme propionate-7 and replacement of the methionine axially bound to the heme iron with a stronger ligand, respectively. The most significant peculiarities with respect to the mammalian analogues include: (i) less negative reduction enthalpies and entropies (Delta S0'rc and Delta H0'rc) for the various protein conformers [low- and high-T native (N1 and N2) and alkaline (A)], whose effects at pH 7 and 25 degrees C largely compensate to produce E degrees ' values very similar to those of the mammalian proteins; (ii) the N1 --> N2 transition that occurs at a lower temperature (e.g., 30-35 degrees C vs 50 degrees C at pH 7. 5) and at a lower pH (7 vs 7.5); and (iii) a more pronounced temperature-induced decrease in the pKa for the alkaline transition which allows observation of the alkaline conformer(s) at pH values as low as 7 upon increasing the temperature above 40 degrees C. Regarding the pH and the temperature ranges of existence of the various protein conformers, these plant cytochromes c are closer to bacterial cytochromes c2.
The effect of membrane chemical composition and drug chemical structure on the localisation of several benzodiazepines (BZDs) (DZ, diazepam; CZ, clonazepam; CX, chlordiazepoxide) within model membranes was investigated. We used a spectrophotometric method presented in a previous paper (B.A. García, M.A. Perillo, Biochim. Biophys. Acta 1324 (1997) 76-84) based on the study of BZD acid-base equilibrium. 'Intrinsic pK' values (pKi) were calculated according to the theory of M.S. Fernández and P. Fromherz (J. Phys. Chem. 81 (1977) 1755-1761). Homogeneous media of known dielectric constant (dioxane 0-80% v/v in water) were used to construct a curve of DeltapKi (pKi-pKw) vs. dielectric constant (D) where DeltapKi values obtained in lipidic dispersions were interpolated. In heterogeneous media consisting of aqueous dispersions of Triton X-100 micelles we determined the relative localisation depth of BZDs according to their DTriton values (36, 37 and 62 for DZ, CX and CZ respectively) taking into account that lower D values correspond to deeper localisation. pKi determined in dispersions of dipalmitoylphosphatidylcholine (dpPC) and egg phosphatidylcholine (egg-PC) mixed multilamellar vesicles showed that, when cholesterol content increased from 0 to 20 mole%, D values decreased (from 59 to 40) in dpPC vesicles and increased (from 51 to 72) in egg-PC vesicles, indicating a tendency of BZDs to penetrate deeper into less ordered interfaces. These results should be considered to understand the non-specific pharmacological effects of BZDs as well as to evaluate the actual relevance of their pharmacological concentrations.