Two types of inositol trisphosphate binding in cardiac microsomes

Kijima, Yoshiyuki; Fleischer, Sidney

doi:10.1016/0006-291x(92)92262-v

Cited by 25 publications

(13 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…2). These values are very similar to values previously reported (21 nM, 0.66 pmol/mg) with canine cardiac microsomes (32) and that of the cloned and expressed type 2 InsP 3 receptor ligand binding domain (27 nM) (6). Although significant variability exists for the reported K D values of the InsP 3 receptors due to differences in purity and experimental conditions, the values obtained in this study are consistent with those of previous studies (6) where membrane preparations and assays were performed us- ing similar methodologies.…”

Section: Panel 2nd Lane)supporting

confidence: 81%

Identification and Functional Reconstitution of the Type 2 Inositol 1,4,5-Trisphosphate Receptor from Ventricular Cardiac Myocytes

Pérez

Ramos-Franco

Fill³

et al. 1997

Journal of Biological Chemistry

145

153

View full text Add to dashboard Cite

The inositol 1,4,5-trisphosphate receptor (InsP 3 R) is an intracellular Ca 2؉ release channel that mediates the rise in cytoplasmic calcium in response to receptor-activated production of InsP 3 . The InsP 3 R-mediated signaling pathway appears to be ubiquitous and is involved in many cellular processes including cell division, smooth muscle contraction, and neuronal signaling. Different regions of the heart also express InsP 3 receptors. We report here that acutely dissociated ventricular myocytes from ferret and rat hearts express significant levels of InsP 3 R as indicated by immunoblotting with a receptor consensus antibody. InsP 3 binding experiments (K D ‫؍‬ 23.6 nM and B max ‫؍‬ 0.46 pmol/mg) suggest the myocytes contain the high affinity type 2 InsP 3 receptor. Exhaustive mRNA screening by polymerase chain reaction, RNase protection, and subsequent DNA sequencing positively identify the InsP 3 R as type 2. The type 2 receptor from ferret heart was then incorporated into planar lipid bilayers and formed Ca 2؉ -selective, InsP 3 -activated, heparin-blocked ion channels. We conclude that the predominant InsP 3 receptor isoform expressed in cardiac myocytes is type 2 and that it forms a functional InsP 3 -gated Ca 2؉ channel when reconstituted in planar lipid bilayers.Inositol 1,4,5-trisphosphate (InsP 3 ) 1 is a well known second messenger mediating the regulated release of intracellular calcium and is produced through the action of phospholipase C. Phospholipase C is activated in response to the stimulation of cell surface receptors coupled to heterotrimeric G-proteins and tyrosine kinases resulting in the hydrolysis of phosphatidylinositol 4,5-bisphosphate to liberate InsP 3 and diacylglycerol. InsP 3 is a readily diffusible compound that binds to specific (InsP 3 R) receptors localized to the endoplasmic reticulum and results in the release of calcium from intracellular stores (see reviews Refs.

show abstract

Section: Panel 2nd Lane)supporting

confidence: 81%

Identification and Functional Reconstitution of the Type 2 Inositol 1,4,5-Trisphosphate Receptor from Ventricular Cardiac Myocytes

Pérez

Ramos-Franco

Fill³

et al. 1997

Journal of Biological Chemistry

145

153

View full text Add to dashboard Cite

show abstract

“…For example, RyR densities amounted to ∼3−4 pmol/mg protein in human ventricle [55,56] and to ∼5.5−7 pmol/mg protein in dog, mouse, rabbit and rat ventricle [56]. IP 3 R densities, on the other hand, were ∼0.09 pmol/mg protein in bovine ventricle [16], 0.66 pmol/mg protein in canine ventricle [32], 0.46 pmol/mg protein in ferret ventricle [57] and 0.35 pmol/mg protein in rat ventricle [58]. Thus, on average there appear to be ∼5−80 times less IP 3 Rs than RyRs in ventricular SR.…”

Section: The Dilemma Of Cardiac Ip 3 Receptors: Lost In An Ocean Of Rmentioning

confidence: 98%

“…This adds to the complexity of IP 3 signaling and suggests that the potential roles of IP 3 go beyond the release of Ca 2+ from internal stores. Higher inositol polyphosphates, including IP 4 , IP 5 and IP 6 , have been detected in the heart [31], as well as high affinity binding sites for IP 4 and IP 6 [32,33]. However, their physiological functions in cardiac myocytes remain poorly understood.…”

Section: The Abc Of Ip 3 : Where Does It Come From and Where Does It Go?mentioning

confidence: 99%

Emerging roles of inositol 1,4,5-trisphosphate signaling in cardiac myocytes

Kockskämper

Zima

Roderick

et al. 2008

Journal of Molecular and Cellular Cardiology

173

149

View full text Add to dashboard Cite

Inositol 1,4,5-trisphosphate (IP 3 ) is a ubiquitous intracellular messenger regulating diverse functions in almost all mammalian cell types. It is generated by membrane receptors that couple to phospholipase C (PLC), an enzyme which liberates IP 3 from phosphatidylinositol 4,5-bisphosphate (PIP 2 ). The major action of IP 3 , which is hydrophilic and thus translocates from the membrane into the cytoplasm, is to induce Ca 2+ release from endogenous stores through IP 3 receptors (IP 3 Rs). Cardiac excitation-contraction coupling relies largely on ryanodine receptor (RyR)-induced Ca 2+ release from the sarcoplasmic reticulum. Myocytes express a significantly larger number of RyRs compared to IP 3 Rs (∼100:1), and furthermore they experience substantial fluxes of Ca 2+ with each heartbeat. Therefore, the role of IP 3 and IP 3 -mediated Ca 2+ signaling in cardiac myocytes has long been enigmatic. Recent evidence, however, indicates that despite their paucity cardiac IP 3 Rs may play crucial roles in regulating diverse cardiac functions. Strategic localization of IP 3 Rs in cytoplasmic compartments and the nucleus enables them to participate in subsarcolemmal, bulk cytoplasmic and nuclear Ca 2+ signaling in embryonic stem cell-derived and neonatal cardiomyocytes, and in adult cardiac myocytes from the atria and ventricles. Intriguingly, expression of both IP 3 Rs and membrane receptors that couple to PLC/IP 3 signaling is altered in cardiac disease such as atrial fibrillation or heart failure, suggesting the involvement of IP 3 signaling in the pathology of these diseases. Thus, IP 3 exerts important physiological and pathological functions in the heart, ranging from the regulation of pacemaking, excitation-contraction and excitation-transcription coupling to the initiation and/or progression of arrhythmias, hypertrophy and heart failure. KeywordsInositol 1,4,5-trisphosphate; Cardiac myocyte; Calcium; Inotropy; Arrhythmias; Nucleus; Hypertrophy © 2008 Elsevier Inc. All rights reserved. * Corresponding author. E-mail address: jens.kockskaemper@meduni-graz.at (J. Kockskämper).. NIH Public Access NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript The discovery of IP 3A quarter of a century ago it was shown that D-myo inositol 1,4,5-trisphosphate (IP 3 ) releases Ca 2+ from a non-mitochondrial internal Ca 2+ store [1]. Since this hallmark discovery, IP 3 has emerged as a ubiquitous intracellular messenger, releasing Ca 2+ from stores through activation of IP 3 receptors (IP 3 Rs) in almost all eukaryotic cells. The major IP 3 -sensitive intracellular Ca 2+ store is the endoplasmic reticulum. However, IP 3 has also been shown to release Ca 2+ stored in other compartments, such as the Golgi and the nuclear envelope [2]. In addition, IP 3 Rs are present on the plasma membrane of some cell types, where they can gate Ca 2+ influx [3]. A crucial role for IP 3 -dependent Ca 2+ release has been demonstrated in many mammalian cell types, ranging from tiny platelets, where it initiates blood clottin...

show abstract

“…If it were, the high [3H]-InsP6 binding density in heart would be consistent with the large number of mitochondria in cardiac myocytes, the mitochondria occupying 32% by volume of rat cardiac muscle (Barth et al, 1992). An alternative intracellular binding site for InsP6 is the sarcoplasmic reticulum since high levels of [3H]-InsP6 binding activity have been observed in a sarcoplasmic reticular fraction of canine heart (Kijima & Fleischer, 1992). The functional role of this binding site is unclear although it may be assumed that it is involved in ionic regulation (Timerman et al, 1992).…”

Section: Localization and Characterization Of [3h]-insp6 Binding In Rmentioning

confidence: 99%

“…Specific, high affinity binding sites for InsP6 were identified in each of these tissues as well as in rat cerebellar homogenates (Hawkins et al, 1990;Poyner et al, 1993). In the only published study of cardiac [3H]-InsP6 binding, a 'receptor' protein with similar properties to that isolated from rat cerebellum (Thiebert et al, 1992) was detected in a microsomal fraction of canine heart homogenates (Kijima & Fleischer, 1992 Worley et al, 1987;. Sections for autoradiography were apposed to Hyperfilm-3H for 4 weeks and processed as described above.…”

Section: Introductionmentioning

confidence: 99%