Cardiac Ca2+ Signaling and Ca2+ Sensitizers

• Endoh Masao

  Department of Cardiovascular Pharmacology, Yamagata University School of Medicine

Bibliographic Information

Other Title

• Cardiac Ca2+ signaling and Ca2+ sesitizers

Abstract

The role of Ca²⁺ in cardiac excitation - contraction (E-C) coupling has been established by simultaneous measurements of contractility and Ca²⁺ transients by means of aequorin in intact myocardium and Ca²⁺ sensitive fluorescent dyes in single myocytes. The E-C coupling process can be classified into 3 processes: upstream (Ca²⁺ mobilization), central (Ca²⁺ binding to troponin C) and downstream mechanism (thin filament regulation and crossbridge cycling). These mechanisms are regulated differentially by various inotropic interventions. Positive force-frequency relationship and effects of β-adrenoceptor stimulation, phosphodiesterase 3 inhibitors and digitalis are essentially exerted via upstream mechanism. Alpha-adrenoceptor stimulation, endothelin-1, angiotensin II, and clinically available Ca²⁺ sensitizers, such as levosimendan and pimobendan, act by a combination of the upstream and central/downstream mechanism. The Frank-Starling mechanism and effects of Ca²⁺ sensitizers such as EMD 57033 and Org 30029 are primarily induced via the central/downstream mechanism. Whereas the upstream and central mechanisms are markedly suppressed in failing myocytes and under acidotic conditions, Ca²⁺ sensitizers such as EMD 57033 and Org 30029 can induce cardiotonic effects under such conditions. Ca²⁺ sensitizers have high therapeutic potential for the treatment of contractile dysfunction in congestive heart failure and ischemic heart diseases, because they have energetic advantages and less risk of Ca²⁺ overload and can maintain effectiveness under pathological conditions. (Circ J 2008; 72: 1915 - 1925)<br>

Journal

• Circulation Journal

  Circulation Journal 72 (12), 1915-1925, 2008

  The Japanese Circulation Society

Keywords

• Calcium
• Congestive heart failure
• Excitation - contraction (E-C) coupling
• Inotropic agents
• Myocardial contraction

Details

• CRID: 1390282680082637440
• NII Article ID: 110006987343
• NII Book ID: AA11591968
• DOI: 10.1253/circj.cj-08-0838
• COI: 1:CAS:528:DC%2BD1MXkt1KqtA%3D%3D
• ISSN: 13474820
• ISSN: 13469843
• PubMed: 18981594
• Web Site: http://www.jstage.jst.go.jp/article/circj/72/12/72_CJ-08-0838/_pdf
• Text Lang: en
• Data Source:
  • JaLC
  • Crossref
  • PubMed
  • CiNii Articles
• Abstract License Flag: Disallowed