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.