Adrenoceptor-mediated regulation of myofibrillar Ca2+ sensitivity through the GTP-binding protein-related mechanisms: Tension recording in β- escin-skinned single rat cardiac cells with preserved receptor functions

Shinji Satoh, Shintaro Kinugawa, Hiroyuki Tsutsui, Akira Takeshita

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

To investigate the mechanisms of receptor-mediated regulation of heart muscle contraction, we developed a tension-recording system using β-escin- skinned single cardiac cells of rats and studied the effects of agonists on myofibrillar Ca2+ sensitivity and Ca2+ release from the sarcoplasmic reticulum (SR): In pCa/tension relations, 1 μM isoproterenol plus 100 μM guanosine 5'-triphosphate (GTP) decreased the myofibrillar Ca2+ sensitivity (pCa50, the [Ca2+] required for half-maximal tension, as an indicator of the sensitivity; from 6.07 to 5.92); this effect was blocked by 1 μM metoprolol or 1 mM guanosine 5'-O-(2-thiodiphosphate) (GDPβS). Phenylephrine (10 μM) plus 100 μM GTP increased the Ca2+ sensitivity (pCa50; from 6.12 to 6.28), and this effect was blocked by 1 μM phentolamine or 1 mM GDPβS. After Ca2+ loading into the SR, 10 μM phenylephrine plus 100 μM GTP in a low-ethylene-glycol-bis(β-aminoethylether)-N,N,N',N'-tetraacetic acid (EGTA, 0.1 mM) relaxing solution induced oscillatory contractions that were attenuated by either 1 μM phentolamine or pre-treatment with 10 μM inositol 1,4,5-trisphosphate. Our results demonstrate that β1-adrenergic stimulation decreases myofibrillar Ca2+ sensitivity and that α1- adrenergic stimulation both increases the Ca2+ sensitivity and activates Ca2+ release from the agonist-sensitive SR through GTP-binding protein- related mechanisms.

Original languageEnglish
Pages (from-to)702-709
Number of pages8
JournalPflugers Archiv European Journal of Physiology
Volume437
Issue number5
DOIs
Publication statusPublished - Apr 16 1999

All Science Journal Classification (ASJC) codes

  • Physiology
  • Clinical Biochemistry
  • Physiology (medical)

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