Abstract
The role of inositol 1,4,5-trisphosphate [Ins(1,4,5)P 3] 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)P 3 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 phyisological relevance of these actions of Ins(1,4,5)P 3 and specifically to test the effect of Ins(1,4,5)P 3 on the Ca2+ sensitivity of Ca2+ release, we compared the effects of Ins(1,4,5)P 3 on Ca2+ oscillations and on Ca2+-induced Ca2+ release (CICR) from the SR in saponin-skinned rat papillary muscle. We found that: (a) 30 μM Ins(1,4,5)P 3 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)P 3 indicating that two different Ca2+-release pools do not exist in cardiac SR; (c) 30 μM Ins(1,4,5)P 3 had no effect on the Ca2+ sensitivity of CICR; (d) Ins(1,4,5)P 3 (up to 30 μM) 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)P 3 hydrolysis. These results suggest that: (a) two different mechanisms underlie Ca2+ oscillations and CICR, Ins(1,4,5)P 3 influencing Ca2+ oscillations but not CICR; (b) Ins(1,4,5)P 3 does not increase the Ca2+ sensitivity of Ca2+ release from the SR; (c) cardiac muscle is different from smooth muscle where Ca2+ release from the SR is dependent upon GTP; (d) the physiological role of Ins(1,4,5)P 3 in excitation-contraction coupling in cardiac muscle is minimal. In contrast, Ins(1,4,5)P 3 may play a pathological role in cardiac arrhythmogenesis by enhancing spontaneous Ca2+ ocsillations.
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Zhu, Y., Nosek, T.M. Inositol trisphosphate enhances Ca2+ oscillations but not Ca2+-induced Ca2+ release from cardiac sarcoplasmic reticulum. Pflügers Archiv 418, 1–6 (1991). https://doi.org/10.1007/BF00370444
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DOI: https://doi.org/10.1007/BF00370444