Published online before print September 4, 2003, doi: 10.1161/01.RES.0000093986.47383.CE
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Submitted on May 23, 2003
Revised on August 22, 2003
Accepted on August 22, 2003
Proton Permeation Through the Myocardial Gap Junction
Massimiliano Zaniboni ;
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.
* To whom correspondence should be addressed. 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 pHi 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 pHi.
Key words: H+ permeation • gap junctions • cardiac myocytes
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