Regular Article
Changes in Ultrastructural Calcium Distribution in Goat Atria During Atrial Fibrillation,☆☆

https://doi.org/10.1006/jmcc.1999.1090Get rights and content

Abstract

It has been suggested that Ca2+content of atrial cardiomyocytes is increased at the onset of atrial fibrillation (AF). Whether this phenomenon is transient is currently unknown. Therefore, in this study the time-related changes in Ca2+location in atrial myocytes from goats with chronic AF have been investigated. The distribution of calcium was assessed with the electron microscope using the cytochemical phosphate-pyroantimonate and oxalate-pyroantimonate methods in atrial biopsies from goats in sinus rhythm and goats with 1–16 weeks of burst-pacing-induced AF. In atrial myocytes from control goats in sinus rhythm, a normal Ca2+distribution was observed, with regular deposits along the sarcolemma (an average of 3.4 deposits per μ m at a regular distance). The number of sarcolemma-bound Ca2+deposits substantially increased after 1 and 2 weeks of atrial fibrillation. After this period the amount of Ca2+precipitate decreased at 4 and 8 weeks, and became below control level at 16 weeks. A similar time-related redistribution of Ca2+occurred in mitochondria. Whereas mitochondria from control goats displayed very few Ca2+deposits (average 4.0 deposits per μ m2), their number markedly increased after 1 and 2 weeks of atrial fibrillation, which indicates cellular Ca2+overload. From 4 weeks, Ca2+deposits reached control levels and were below control level after 16 weeks of atrial fibrillation (2.5 deposits per μ m2). Our findings are consistent with the previously observed Ca2+overload early after the onset of atrial fibrillation. The present study shows that this overload persists for at least 2 weeks, after which the cardiomyocytes apparently adapt to a new Ca2+homeostasis, thereby avoiding Ca2+overload. This protection against Ca2+overload co-occurs with dedifferentiation like cellular remodeling.

References (40)

  • J Ausma et al.

    Dedifferentiation of atrial cardiomyocytes as a result of chronic atrial fibrillation

    Am J Pathol

    (1997)
  • J Ausma et al.

    Time course of structural changes due to atrial fibrillation in the goat

    Circulation

    (1998)
  • W Manning et al.

    Impaired left atrial mechanical function after cardioversion: relation to the duration of atrial fibrilation

    J Am Coll Cardiol

    (1994)
  • E Leistad et al.

    Atrial contractile dysfunction after short-term atrial fibrillation is reduced by verapamil, but increased by BAY-K 8644

    Circulation

    (1996)
  • RG Tieleman et al.

    Verapamil reduces tachycardia-induced electrical remodeling of the atria

    Circulation

    (1997)
  • A Goette et al.

    Electrical remodeling in atrial fibrillation. Time course and mechanisms

    Circulation

    (1996)
  • EG Daoud et al.

    Effect of verapamil and procainamide on atrial fibrillation-induced electrical remodeling in humans

    Circulation

    (1997)
  • W Flameng et al.

    Cardioprotective effects of lidoflazine during 1 hour normothermic ischemia

    Circulation

    (1981)
  • M Borgers et al.

    Distribution of calcium in a subset of chronic hibernating myocardium in man

    Histochem J

    (1993)
  • M Borgers et al.

    Changes in ultrastructure and Ca2+distribution in the isolated working rabbit heart after ischemia

    Am J Pathol

    (1987)
  • Cited by (87)

    • Mechanism and Prevention of Atrial Remodeling and Their Related Genes in Cardiovascular Disorders

      2023, Current Problems in Cardiology
      Citation Excerpt :

      Rapid depolarization of atrial myocytes during AF prolongs atrial systole, promotes calcium influx through calcium overload and leads to calcium release from sarcoplasmic reticulum calcium pool.26,27 Ausma et al.26 found that the content of muscle fiber membrane and mitochondrial membrane binding protein increased in the first 2 weeks of AF; the calcium content began to decrease at 4 weeks; At 16 weeks, the calcium content was close to or even lower than normal. It has been found that structural remodeling in AF is related to the hydrolysis of calcium activated proteins.

    • Redox control of cardiac remodeling in atrial fibrillation

      2015, Biochimica et Biophysica Acta - General Subjects
      Citation Excerpt :

      A consistent model of AngII and β1-adrenergic stimulated, protein kinase-dependent oxidative regulation of the cardiac Na+–K+ pump has been proposed, which indeed has important implications for cardiac physiology and disease, including AF [233]. Studies on atrial tissue have shown that an AF- or RAP-induced calcium-overload of cardiomyocytes induces ultrastructural alterations including morphologically altered mitochondria [20,21,28,234]. AF is associated with a higher demand of energy of cardiomyocytes resulting in transiently decreased concentrations of high energy phosphates and mitochondrial NADH [28,234].

    • Mechanisms of Arrhythmias and Conduction Disorders in Older Adults

      2012, Clinics in Geriatric Medicine
      Citation Excerpt :

      These changes in electrophysiologic properties of the atrium, termed “electrical remodeling,” likely result from reduction in the L-type Ca2+ current and transient outward K+ current, a progressive late reduction in the density of voltage-gated Na+ channels, and gap junction redistribution that contributes to the slowing of conduction, thus increasing vulnerability of the atria to reentry and creating a condition in which AF perpetuates AF.79,102,106,107 These electrophysiologic changes are different from structural changes that are observed in patients with heart failure or in the senescent atria with gradual loss of myofibrils, myocyte hypertrophy, fragmentation of sarcoplasmic reticulum, and fibrosis with changes in the structure and shape of mitochondria.1,46,62,108–117 Changes in protein expression, similar to a de-differentiation process toward a partially fetal phenotype or that seen in hibernating myocardium, also take place with chronic AF.108,110

    • Increased Expression of Mineralocorticoid Receptor in Human Atrial Fibrillation and a Cellular Model of Atrial Fibrillation

      2010, Journal of the American College of Cardiology
      Citation Excerpt :

      In our cellular AF model, intracellular calcium concentration was elevated by rapid depolarization (6). This result is similar to that found in a rapid-pacing model of AF (18). We also showed that intracellular calcium chelator BAPTA-AM and the L-type calcium-channel blocker verapamil abolished rapid depolarization-induced increment of MR expression.

    View all citing articles on Scopus

    Please address all correspondence to: Dr J. Ausma, Dept of Physiology, Maastricht University, P.O. Box 616, 6200 MD Maastricht, The Netherlands. E-mail: [email protected]

    ☆☆

    This study was presented in part at the 71st Annual Scientific Sessions of the American Heart Association (Circulation Vol 98, I-683, 1998).

    View full text