Oxygen Wasting for Ca2+ Extrusion Activated by Partial Inhibition of Sarcoplasmic Reticulum Ca2+-ATPase by Cyclopiazonic Acid in Rat Left Ventricles.

• Misawa Hiromi

  Department of Physiology II, Nara Medical University

• Kohzuki Hisaharu

• Sakata Susumu

• Ohga Yoshimi

• Takaki Miyako

Bibliographic Information

Other Title

• Oxygen Wasting for Ca〔2+〕 Extrusion Activated by Partial Inhibition of Sarcoplasmic Reticulum Ca〔2+〕-ATPase by Cyclopiazonic Acid in Rat Left Ventricles

Abstract

In the excised Langendorff-perfused rat whole-heart preparation, a linear relation between left ventricular myocardial oxygen consumption per beat (Vo₂) and systolic pressure-volume area (PVA, a total mechanical energy per beat) is obtained from a curved end-systolic pressure-volume relation as in the blood-perfused preparation. The ordinate Vo₂ intercept of the Vo₂-PVA relation is composed of Vo₂ for total Ca²⁺ handling in the excitation-contraction coupling and basal metabolism. The Vo₂ for total Ca²⁺ handling is mainly consumed by sarcoplasmic reticulum (SR) Ca²⁺-ATPase. The aim of the present study was to investigate, in terms of left ventricular mechanoenergetics, how an inhibition of SR Ca²⁺-ATPase by cyclopiazonic acid (CPA; 4 μmol/l) affects Ca²⁺ handling mechanisms in the excised Langendorff-perfused rat whole-heart preparation. The short-term (for 3 to 6 min after onset of the infusion) CPA infusion decreased Vo₂ proportionally to the decrease in PVA. The long-term (for 9 to 12 min after the short-term CPA infusion) CPA infusion gradually increased Vo₂ almost to the control level with an increase in PVA. The increases in both Vo₂ and PVA during this infusion were completely abolished by a Na⁺/Ca²⁺ exchanger inhibitor, 3′9,4′9-dichlorobenzamil, indicating the contribution of Na⁺/Ca²⁺ exchanger to the increases in Vo₂ and PVA. The O₂ cost of left ventricular contractility during the long-term CPA infusion was significantly higher than during the short-term CPA infusion. All these results suggest the possibility of the contribution of greater energy–wasting Ca²⁺ extrusion processes (such as Na⁺/K⁺-ATPase coupled to the Na⁺/Ca²⁺ exchanger; its stoichiometry is 1 ATP : 1 Ca²⁺) to the larger oxygen cost of left ventricular contractility.<br>

Journal

• The Japanese Journal of Physiology

  The Japanese Journal of Physiology 51 (1), 99-108, 2001

  THE PHYSIOLOGICAL SOCIETY OF JAPAN

Keywords

• cyclopiazonic acid
• O<SUB>2</SUB> consumption
• sarcolemmal Na<SUP>+</SUP>/Ca<SUP>2+</SUP> exchanger
• sarcoplasmic reticulum Ca<SUP>2+</SUP>-ATPase

Details

• CRID: 1390282680017740544
• NII Article ID: 130004435754
• NII Article ID: 10008293063
• NII Book ID: AA00691224
• DOI: 10.2170/jjphysiol.51.99
• COI: 1:CAS:528:DC%2BD3MXivVGktr0%3D
• ISSN: 18811396
• ISSN: 0021521X
• NDL BIB ID: 5739143
• PubMed: 11282001
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I5739143
• Web Site: https://search.jamas.or.jp/link/ui/2001199961
• Text Lang: en
• Data Source:
  • JaLC
  • NDL
  • Crossref
  • PubMed
  • CiNii Articles
• Abstract License Flag: Disallowed