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Abstract #3943

An Extra-Mitochondrial Domain Rich in Carbonic Anhydrase Activity Improves Myocardial Energetics

Marie A. Schroeder1, Mohammad Ali1, Alzbeta Hulikova1, Claudiu T. Supuran2, Kieran Clarke1, Richard D. Vaughan-Jones1, Damian J. Tyler1, Pawel Swietach1

1Physiology, Anatomy and Genetics, University of Oxford, Oxford, Oxon, United Kingdom; 2University of Florence, Florence, Italy

CO2 is produced in vast quantities by cardiac mitochondria and efficient means of its venting are required to support metabolism. A range of metabolic and physiological adaptations for improving energy provision has been identified1, yet little is known about mechanisms for improving CO2 venting. Carbonic anhydrases (CAs), expressed at various sites in ventricular cardiomyocytes, may affect mitochondrial CO2 clearance by catalyzing CO2 hydration (to H+ and HCO3−) and changing trans-membrane [CO2]-gradients for diffusion. In this study, we demonstrated that mitochondrial CO2 venting is facilitated by concentrating CA activity near (but not within) mitochondria, and that this distribution improves myocardial energetics.