Slc26a6 functions as an electrogenic Cl/HCO3 exchanger in cardiac myocytes

Alterations in cardiac acidbase balance can produce profound impact on excitationcontraction coupling and precipitate cardiac dysfunction and arrhythmias. A member of the solute carrier (SLC) family, Slc26a6, has been shown to be a chloride-hydroxyl exchanger and the predominant chloride-bicarbonate exchanger in the mouse heart. However, the exact isoforms and functional characteristics of cardiac Slc26a6 remain unknown. The objective of the present study is to determine the molecular identity of cardiac Slc26a6 isoforms, to examine their cellular expressions in the heart, and to test the function of Slc26a6 in cardiomyocytes. We examined the expression and function of slc26a6 in mouse cardiomyocytes using RTPCR, immunofluorescence confocal microscopy, and patch-clamp technique coupled with the fast solution exchange system. We identified four cardiac Slc26a6 isoforms, denoted C-a, C-b, C-c, and C-d, and detected significant expression of Slc26a6 in the plasma membrane of both atrial and ventricular myocytes. Isoforms C-a and C-b share the same sequence with the previously reported murine Slc26a6a and Slc26a6b, respectively. Isoform C-c lacks an alternate in-frame exon 12, whereas C-d is a C-terminal truncated form resulting from 102 bp exon insertion between exons 15 and 16 compared with C-b. Patch-clamp recordings demonstrated electrogenic Cl/oxalate and electrogenic Cl/HCO3 exchange activities in cardiomyocytes. We demonstrate that cardiac myocytes express different isoforms of Slc26a6, which encode electrogenic Cl/HCO3 and Cl/oxalate exchangers. The electrogenic nature of the Cl/HCO3 exchange of cardiac Slc26a6 suggests important roles in regulating acidbase balance in the heart.