Inositol trisphosphate enhances Ca2+ oscillations but not Ca(2+)-induced Ca2+ release from cardiac sarcoplasmic reticulum.
The role of inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] in excitation-contraction coupling in cardiac muscle is still unclear, although many laboratories are beginning to assume a critical role for this putative second messenger. Earlier studies from this laboratory [Nosek et al. (1986) Am J Physiol 250:C807] found that Ins(1,4,5)P3 enhanced spontaneous Ca2+ release and the caffeine sensitivity of Ca2+ release from myocardial sarcoplasmic reticulum (SR) and proposed an increase in the Ca2+ sensitivity of the release as a possible mechanism. In order to clarify the physiological relevance of these actions of Ins(1,4,5)P3 and specifically to test the effect of Ins(1,4,5)P3 on the Ca2+ sensitivity of Ca2+ release, we compared the effects of Ins(1,4,5)P3 on Ca2+ oscillations and on Ca(2+)-induced Ca2+ release (CICR) from the SR in saponin-skinned rat papillary muscle. We found that: (a) 30 microM Ins(1,4,5)P3 enhanced the Ca2+ oscillations (measured by tension oscillations) from the rat cardiac SR, consistent with the previous report on guinea pig tissue; (b) both GTP and GTP[S] enhanced Ca2+ oscillations. The effect was not additive to that of Ins(1,4,5)P3 indicating that two different Ca(2+)-release pools do not exist in cardiac SR; (c) 30 microM Ins(1,4,5)P3 had no effect on the Ca2+ sensitivity of CICR; (d) Ins(1,4,5)P3 (up to 30 microM) had no effect on SR Ca2+ loading. The studies were performed in the presence of Cd2+ or 2,3-bisphosphoglycerate, agents that inhibit Ins(1,4,5)P3 hydrolysis.(ABSTRACT TRUNCATED AT 250 WORDS)
Zhu
Y
Y
Department of Physiology and Endocrinology, Medical College of Georgia, Augusta 30912-3000.
Nosek
T M
TM
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015544:Inositol 1,4,5-Trisphosphate / Q000502:physiology*; D007700:Kinetics; D009206:Myocardium / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012519:Sarcoplasmic Reticulum / Q000378:metabolism*
D015544:Inositol 1,4,5-Trisphosphate; D002118:Calcium