Modulation of sarcoplasmic reticulum Ca(2+)-release channels by caffeine, Ca2+, and Mg2+ in skinned myocardial fibers of fetal and adult rats.
Ryanodine causes depression of the caffeine-induced tension transient (ryanodine depression) in skinned muscle fibers, because it blocks the sarcoplasmic reticulum (SR) Ca(2+)-release channels [Su, J. Y. (1988) Pflügers Arch 411:132-136, 371-377; (1992) Pflügers Arch 421:1-6]. This study was performed to examine the sensitivity of SR Ca(2+)-release channels to ryanodine in fetal compared to adult myocardium and to investigate the influence of Ca2+, caffeine, and Mg2+ on ryanodine depression in skinned fibers. Ryanodine (0.3 nM-1 microM) caused a dose-dependent depression in skinned myocardial fibers of the rat, and the fetal fibers (IC50 approximately 74 nM) were 26-fold less sensitive than those of the adult (IC50 approximately 2.9 nM). The depression induced by 0.1 microM or 1 microM ryanodine was a function of [caffeine], or [Ca2+] (pCa < 6.0), which was potentiated by caffeine, and an inverse function of [Mg2+]. At pCa > 8.0 plus 25 mM caffeine, a 20% ryanodine depression was observed in both the fetal and adult fibers, indicating independence from Ca2+. Ryanodine depression in skinned fibers of the fetus was less affected than that seen in the adult by pCai, [caffeine]i, or 25 mM caffeine plus pCai or plus pMgi (IC50 approximately pCa 4.5 versus 5.1; caffeine 12.7 mM versus 2 mM; pCa 6.7 versus 7.3; and pMg 3.9 versus 3.3 respectively). The results show that the SR Ca(2+)-release channel in both fetal and adult myocardium is modulated by Ca2+, caffeine, and Mg2+.(ABSTRACT TRUNCATED AT 250 WORDS)
Su
J Y
JY
Department of Anesthesiology, University of Washington, Seattle 98195.
Chang
Y I
YI
D000818:Animals; D002110:Caffeine / Q000008:administration & dosage / Q000494:pharmacology*; D002118:Calcium / Q000008:administration & dosage / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006321:Heart / Q000196:embryology / Q000254:growth & development / Q000502:physiology; D008274:Magnesium / Q000494:pharmacology*; D009200:Myocardial Contraction / Q000187:drug effects*; D011247:Pregnancy; D051381:Rats; D012433:Ryanodine / Q000494:pharmacology; D012519:Sarcoplasmic Reticulum / Q000502:physiology*
D015220:Calcium Channels; D012433:Ryanodine; D002110:Caffeine; D008274:Magnesium; D002118:Calcium