Reducing Ryanodine Receptor Open Probability as a Means to Abolish Spontaneous Ca ²⁺ Release and Increase Ca ²⁺ Transient Amplitude in Adult Ventricular Myocytes

• L.A. Venetucci

  From the Unit of Cardiac Physiology, University of Manchester, United Kingdom. Present address for M.E.D.: Veterinary Biomedical Sciences, Royal (Dick) School of Veterinary Studies, The University of Edinburgh, United Kingdom.

• A.W. Trafford

  From the Unit of Cardiac Physiology, University of Manchester, United Kingdom. Present address for M.E.D.: Veterinary Biomedical Sciences, Royal (Dick) School of Veterinary Studies, The University of Edinburgh, United Kingdom.

• M.E. Díaz

  From the Unit of Cardiac Physiology, University of Manchester, United Kingdom. Present address for M.E.D.: Veterinary Biomedical Sciences, Royal (Dick) School of Veterinary Studies, The University of Edinburgh, United Kingdom.

• S.C. O’Neill

  From the Unit of Cardiac Physiology, University of Manchester, United Kingdom. Present address for M.E.D.: Veterinary Biomedical Sciences, Royal (Dick) School of Veterinary Studies, The University of Edinburgh, United Kingdom.

• D.A. Eisner

  From the Unit of Cardiac Physiology, University of Manchester, United Kingdom. Present address for M.E.D.: Veterinary Biomedical Sciences, Royal (Dick) School of Veterinary Studies, The University of Edinburgh, United Kingdom.

抄録

The aim of this work was to investigate whether it is possible to remove arrhythmogenic Ca 2+ release from the sarcoplasmic reticulum that occurs in calcium overload without compromising normal systolic release. Exposure of rat ventricular myocytes to isoproterenol (1 μmol/L) resulted in an increased amplitude of the systolic Ca 2+ transient and the appearance of waves of diastolic Ca 2+ release. Application of tetracaine (25 to 50 μmol/L) decreased the frequency or abolished the diastolic Ca 2+ release. This was accompanied by an increase in the amplitude of the systolic Ca 2+ transient. Cellular Ca 2+ flux balance was investigated by integrating Ca 2+ entry (on the L-type Ca 2+ current) and efflux (on Na–Ca 2+ exchange). Isoproterenol increased Ca 2+ influx but failed to increase Ca 2+ efflux during systole (because of the abbreviation of the duration of the Ca 2+ transient). To match this increased influx the bulk of Ca 2+ efflux occurred via Na–Ca 2+ exchange during a diastolic Ca 2+ wave. Subsequent application of tetracaine increased systolic Ca 2+ efflux and abolished the diastolic efflux. The increase of systolic efflux in tetracaine resulted from both increased amplitude and duration of the systolic Ca 2+ transient. In the presence of isoproterenol, those Ca 2+ transients preceded by diastolic release were smaller than those where no diastolic release had occurred. When tetracaine was added, the amplitude of the Ca 2+ transient was similar to those in isoproterenol with no diastolic release and larger than those preceded by diastolic release. We conclude that tetracaine increases the amplitude of the systolic Ca 2+ transient by removing the inhibitory effect of diastolic Ca 2+ release.

収録刊行物

• Circulation Research

  Circulation Research 98 (10), 1299-1305, 2006-05-26

  Ovid Technologies (Wolters Kluwer Health)

キーワード

• Cardiology and Cardiovascular Medicine
• Physiology

詳細情報

• CRID: 1363107369931325184
• NII論文ID: 30022676256
• DOI: 10.1161/01.res.0000222000.35500.65
• ISSN: 15244571
• ISSN: 00097330
• ISSN: http://id.crossref.org/issn/00097330
• Web Site: https://www.ahajournals.org/doi/full/10.1161/01.RES.0000222000.35500.65
• データソース種別:
  • Crossref
  • CiNii Articles