Carbonic anhydrase inhibitors modify intracellular pH transients and contractions of rat middle cerebral arteries during CO2/HCO3– fluctuations
| Autor: | Ebbe Boedtkjer, Jacob Korsbæk Rasmussen |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
biology Intracellular pH Cerebral arteries 03 medical and health sciences Cytosol 030104 developmental biology Membrane Neurology Biochemistry Carbonic anhydrase medicine biology.protein Biophysics Extracellular Neurology (clinical) medicine.symptom Cardiology and Cardiovascular Medicine Vasoconstriction Intracellular |
| Zdroj: | Rasmussen, J K & Boedtkjer, E 2018, ' Carbonic anhydrase inhibitors modify intracellular pH transients and contractions of rat middle cerebral arteries during CO 2 /HCO 3 – fluctuations ', Journal of Cerebral Blood Flow and Metabolism, vol. 38, no. 3, pp. 492-505 . |
| ISSN: | 1559-7016 0271-678X |
| Popis: | The CO2/HCO3– buffer minimizes pH changes in response to acid–base loads, HCO3– provides substrate for Na+,HCO3–-cotransporters and Cl–/HCO3–-exchangers, and H+ and HCO3– modify vasomotor responses during acid–base disturbances. We show here that rat middle cerebral arteries express cytosolic, mitochondrial, extracellular, and secreted carbonic anhydrase isoforms that catalyze equilibration of the CO2/HCO3– buffer. Switching from CO2/HCO3–-free to CO2/HCO3–-containing extracellular solution results in initial intracellular acidification due to hydration of CO2 followed by gradual alkalinization due to cellular HCO3– uptake. Carbonic anhydrase inhibition decelerates the initial acidification and attenuates the associated transient vasoconstriction without affecting intracellular pH or artery tone at steady-state. Na+,HCO3–-cotransport and Na+/H+-exchange activity after NH4+-prepulse-induced intracellular acidification are unaffected by carbonic anhydrase inhibition. Extracellular surface pH transients induced by transmembrane NH3 flux are evident under CO2/HCO3–-free conditions but absent when the buffer capacity and apparent H+ mobility increase in the presence of CO2/HCO3– even after the inhibition of carbonic anhydrases. We conclude that (a) intracellular carbonic anhydrase activity accentuates pH transients and vasoconstriction in response to acute elevations of pCO2, (b) CO2/HCO3– minimizes extracellular surface pH transients without requiring carbonic anhydrase activity, and (c) carbonic anhydrases are not rate limiting for acid–base transport across cell membranes during recovery from intracellular acidification. |
| Databáze: | OpenAIRE |
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