Proton permeation through the myocardial gap junction.
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).
Zaniboni
Massimiliano
M
Burdon Sanderson Cardiac Science Centre, University Laboratory of Physiology, Parks Road, Oxford OX1 3PT, UK.
Rossini
Alessandra
A
Swietach
Pawel
P
Banger
Nurindura
N
Spitzer
Kenneth W
KW
Vaughan-Jones
Richard D
RD
D000818:Animals; D001578:Benzopyrans; D002463:Cell Membrane Permeability / Q000187:drug effects; D002478:Cells, Cultured; D017097:Electric Impedance; D005456:Fluorescent Dyes; D017629:Gap Junctions / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D006034:Glycyrrhetinic Acid / Q000494:pharmacology; D006168:Guinea Pigs; D006863:Hydrogen-Ion Concentration; D015640:Ion Channel Gating; D017136:Ion Transport; D007700:Kinetics; D018613:Microscopy, Confocal; D008954:Models, Biological; D009206:Myocardium / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D009284:Naphthols; D017494:Proton Pumps / Q000378:metabolism; D011522:Protons; D012235:Rhodamines; D012508:Sarcolemma / Q000737:chemistry / Q000187:drug effects
D001578:Benzopyrans; D005456:Fluorescent Dyes; D009284:Naphthols; D017494:Proton Pumps; D011522:Protons; D012235:Rhodamines; C068301:carboxy-seminaphthorhodaminefluoride; D006034:Glycyrrhetinic Acid