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

Hyo Jeong Kim, Richard Myers, Choong Ryoul Sihn, Sassan Rafizadeh, Xiao Dong Zhang

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Aims: Alterations in cardiac acid-base balance can produce profound impact on excitation-contraction 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. Methods and results: We examined the expression and function of slc26a6 in mouse cardiomyocytes using RT-PCR, 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-/HCO 3 - exchange activities in cardiomyocytes. Conclusion: 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 acid-base balance in the heart.

Original languageEnglish (US)
Pages (from-to)383-391
Number of pages9
JournalCardiovascular research
Volume100
Issue number3
DOIs
StatePublished - Dec 1 2013

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Chloride-Bicarbonate Antiporters
Cardiac Myocytes
Protein Isoforms
Exons
Oxalates
Acid-Base Equilibrium
Heart Function Tests
Excitation Contraction Coupling
Patch-Clamp Techniques
Fluorescence Microscopy
Confocal Microscopy
Hydroxyl Radical
Muscle Cells
Cardiac Arrhythmias
Chlorides
Cell Membrane
Polymerase Chain Reaction

Keywords

  • Acid-base balance
  • Cardiomyocytes
  • P H
  • Slc26a6
  • Solute carrier

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Slc26a6 functions as an electrogenic Cl/HCO3 exchanger in cardiac myocytes. / Kim, Hyo Jeong; Myers, Richard; Sihn, Choong Ryoul; Rafizadeh, Sassan; Zhang, Xiao Dong.

In: Cardiovascular research, Vol. 100, No. 3, 01.12.2013, p. 383-391.

Research output: Contribution to journalArticle

Kim, Hyo Jeong ; Myers, Richard ; Sihn, Choong Ryoul ; Rafizadeh, Sassan ; Zhang, Xiao Dong. / Slc26a6 functions as an electrogenic Cl/HCO3 exchanger in cardiac myocytes. In: Cardiovascular research. 2013 ; Vol. 100, No. 3. pp. 383-391.
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abstract = "Aims: Alterations in cardiac acid-base balance can produce profound impact on excitation-contraction 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. Methods and results: We examined the expression and function of slc26a6 in mouse cardiomyocytes using RT-PCR, 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-/HCO 3 - exchange activities in cardiomyocytes. Conclusion: 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 acid-base balance in the heart.",
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AU - Kim, Hyo Jeong

AU - Myers, Richard

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AU - Rafizadeh, Sassan

AU - Zhang, Xiao Dong

PY - 2013/12/1

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N2 - Aims: Alterations in cardiac acid-base balance can produce profound impact on excitation-contraction 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. Methods and results: We examined the expression and function of slc26a6 in mouse cardiomyocytes using RT-PCR, 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-/HCO 3 - exchange activities in cardiomyocytes. Conclusion: 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 acid-base balance in the heart.

AB - Aims: Alterations in cardiac acid-base balance can produce profound impact on excitation-contraction 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. Methods and results: We examined the expression and function of slc26a6 in mouse cardiomyocytes using RT-PCR, 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-/HCO 3 - exchange activities in cardiomyocytes. Conclusion: 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 acid-base balance in the heart.

KW - Acid-base balance

KW - Cardiomyocytes

KW - P H

KW - Slc26a6

KW - Solute carrier

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