Intracellular chloride accumulation and subcellular elemental distribution during atrial fibrillation

Joseph G. Akar, Thomas Everett, Ruoya Ho, Joseph Craft, David E. Haines, Andrew P. Somlyo, Avril V. Somlyo

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Background - Ion channel remodeling occurs during atrial fibrillation (AF); however, the extent of alteration in the subcellular distribution of elements (Na, K, Cl, Ca, Mg, P) is unknown. Electron probe microanalysis was used to determine the total (free+bound) in vivo subcellular concentration of these elements during AF. Methods and Results - The left atrial appendage (LAA) was snap-frozen in situ after pacing (640 bpm) for 3 minutes (n=5 dogs), 30 minutes (n=3), or 48 hours (n=5). Dogs in sinus rhythm (n=3) served as controls. Whole-cell, cytosolic, and mitochondrial elemental concentrations were measured in cryosections. LAA effective refractory period (ERP) was measured before and after pacing. LAA ERP decreased significantly after 48 hours (116±3 to 88±10 ms, P=0.02). Whole-cell Cl increased by 9.0 mmol/L and 17 mmol/L after 3 and 30 minutes of pacing, respectively (P<0.0001), without a concomitant increase in Na. However, at 48 hours, whole-cell Na was reduced by 51% (P<0.01). Cytosolic Ca increased by 1.1 mmol/kg dry wt after 3 minutes (P<0.005), but mitochondrial Ca remained low and unchanged. Cell size measured in transverse cryosections increased after 3 minutes of pacing (75±5 to 109±11 μm2, P=0.007) but returned to baseline by 30 minutes (66±5 μm2). Conclusions - Intracellular Cl accumulation induced by rapid pacing is a novel finding and may play a role in AF pathogenesis by causing resting membrane depolarization and ERP reduction. There was no evidence of cellular or mitochondrial Ca overload despite the development of electrical remodeling and transient increase in cytoplasmic Ca.

Original languageEnglish (US)
Pages (from-to)1810-1815
Number of pages6
JournalCirculation
Volume107
Issue number13
DOIs
StatePublished - Apr 8 2003
Externally publishedYes

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Atrial Appendage
Atrial Fibrillation
Chlorides
Dogs
Atrial Remodeling
Electron Probe Microanalysis
Ion Channels
Cell Size
Membranes

Keywords

  • Calcium
  • Chloride
  • Electron probe microanalysis
  • Fibrillation
  • Pacing

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Intracellular chloride accumulation and subcellular elemental distribution during atrial fibrillation. / Akar, Joseph G.; Everett, Thomas; Ho, Ruoya; Craft, Joseph; Haines, David E.; Somlyo, Andrew P.; Somlyo, Avril V.

In: Circulation, Vol. 107, No. 13, 08.04.2003, p. 1810-1815.

Research output: Contribution to journalArticle

Akar, Joseph G. ; Everett, Thomas ; Ho, Ruoya ; Craft, Joseph ; Haines, David E. ; Somlyo, Andrew P. ; Somlyo, Avril V. / Intracellular chloride accumulation and subcellular elemental distribution during atrial fibrillation. In: Circulation. 2003 ; Vol. 107, No. 13. pp. 1810-1815.
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AU - Akar, Joseph G.

AU - Everett, Thomas

AU - Ho, Ruoya

AU - Craft, Joseph

AU - Haines, David E.

AU - Somlyo, Andrew P.

AU - Somlyo, Avril V.

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AB - Background - Ion channel remodeling occurs during atrial fibrillation (AF); however, the extent of alteration in the subcellular distribution of elements (Na, K, Cl, Ca, Mg, P) is unknown. Electron probe microanalysis was used to determine the total (free+bound) in vivo subcellular concentration of these elements during AF. Methods and Results - The left atrial appendage (LAA) was snap-frozen in situ after pacing (640 bpm) for 3 minutes (n=5 dogs), 30 minutes (n=3), or 48 hours (n=5). Dogs in sinus rhythm (n=3) served as controls. Whole-cell, cytosolic, and mitochondrial elemental concentrations were measured in cryosections. LAA effective refractory period (ERP) was measured before and after pacing. LAA ERP decreased significantly after 48 hours (116±3 to 88±10 ms, P=0.02). Whole-cell Cl increased by 9.0 mmol/L and 17 mmol/L after 3 and 30 minutes of pacing, respectively (P<0.0001), without a concomitant increase in Na. However, at 48 hours, whole-cell Na was reduced by 51% (P<0.01). Cytosolic Ca increased by 1.1 mmol/kg dry wt after 3 minutes (P<0.005), but mitochondrial Ca remained low and unchanged. Cell size measured in transverse cryosections increased after 3 minutes of pacing (75±5 to 109±11 μm2, P=0.007) but returned to baseline by 30 minutes (66±5 μm2). Conclusions - Intracellular Cl accumulation induced by rapid pacing is a novel finding and may play a role in AF pathogenesis by causing resting membrane depolarization and ERP reduction. There was no evidence of cellular or mitochondrial Ca overload despite the development of electrical remodeling and transient increase in cytoplasmic Ca.

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KW - Chloride

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KW - Fibrillation

KW - Pacing

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