Marie Allen Schroeder1, Pawel Swietach1, Philip Lee2, Ferdia A. Gallagher3,4, Ben Rowlands1, Claudiu T. Supuran5, Kevin M. Brindle, 4,6, Richard D. Vaughan-Jones1, George K. Radda1,2, Kieran Clarke1, Damian J. Tyler1
1Physiology, Anatomy and Genetics, University of Oxford, Oxford, Oxfordshire, United Kingdom; 2Biomedical Sciences Institute, Singapore Bioimaging Consortium, Singapore, Singapore; 3Radiology, Addenbrooke's Hospital, University of Cambridge, Cambridge, United Kingdom; 4Li Ka Shing Centre, CRUK Cambridge Research Institute, Cambridge, United Kingdom; 5Dipartimento di Chimica, University of Florence, Florence, Italy; 6Biochemistry, University of Cambridge, Cambridge, United Kingdom
Carbonic anhydrase (CA) catalyses the hydration of CO2 to form HCO3- and H+, an inter-conversion which serves as a major pH buffer in blood plasma and inside cells. To date, cardiac isoforms of CA have only been studied in vitro, where their function could be drastically different than in vivo. The aim of this study was to determine the effects of intra- and extracellular isoforms of CA on CO2 efflux from the heart, in vivo, based on MRS detection of 13CO2 generated from the metabolism of hyperpolarised [1-13C]pyruvate. Our results indicated that extracellular CAs do not affect cardiac CO3 removal under control perfusion conditions, though may have a role in ischemia. Further, we observed that intracellular CA activity trapped HCO3- and H+ within the myocyte, which could potentially acidify the intracellular space. Physiological levels of cardiac intracellular CA must balance retention of myocardial bicarbonate to buffer potential acid/base disturbances, without causing excessive intracellular acidification.