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(Circulation Research. 2003;93:726.)
© 2003 American Heart Association, Inc.

Cellular Biology

Proton Permeation Through the Myocardial Gap Junction

Massimiliano Zaniboni, Alessandra Rossini, Pawel Swietach, Nurindura Banger, Kenneth W. Spitzer, Richard D. Vaughan-Jones

From the Burdon Sanderson Cardiac Science Centre (M.Z., A.R., P.S., N.B., R.D.V.-J.), University Laboratory of Physiology, Oxford, UK; Dipartimento di Biologia Evolutiva e Funzionale (M.Z., A.R.), University of Parma, Parma, Italy; Nora Eccles Harrison Cardiovascular Research and Training Institute (K.W.S.), University of Utah, Salt Lake City, Utah.

Correspondence to Prof Richard D. Vaughan-Jones, Burdon Sanderson Cardiac Science Centre, University Laboratory of Physiology, Parks Road, Oxford OX1 3PT, UK. E-mail richard.vaughan-jones{at}physiol.ox.ac.uk

Although protons can directly or indirectly gate solute permeability of the myocardial gap junction, there is little information regarding their own permeation, despite their importance in the regulation of myocardial contractility and rhythm. By pipette-loading of acid into guinea pig isolated, ventricular myocyte pairs while imaging pH_i confocally using SNARF fluorescence, we have observed that protons permeate the junctional region. Permeation is inhibited by glycyrrhetinic acid, an agent that also increases intercellular electrical resistance, suggesting H⁺ permeation via gap junctions. The rate of spread of acid between cells appears to be limited by junctional permeation rather than by cytoplasmic diffusion. Mathematical analyses, combined with experiments using SNARF as a proton carrier, suggest that gap junctional H⁺ transmission may be accomplished physiologically by the permeation of intrinsic "proton-porter" molecules. We propose that proton flux through gap junctions will contribute to the dissipation of regional acid loads within the myocardium. This represents a mechanism for the local control of myocardial pH_i.

Key Words: H⁺ permeation • gap junctions • cardiac myocytes

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