Transient receptor potential M3 channels are ionotropic steroid receptors in pancreatic β cells

2008 ◽  
Vol 10 (12) ◽  
pp. 1421-1430 ◽  
Author(s):  
Thomas F.J. Wagner ◽  
Sabine Loch ◽  
Sachar Lambert ◽  
Isabelle Straub ◽  
Stefanie Mannebach ◽  
...  
Keyword(s):  
Transient Receptor Potential ◽  
Steroid Receptors ◽  
Receptor Potential ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Transient Receptor

scholarly journals TRPV2 channels mediate insulin secretion induced by cell swelling in mouse pancreatic β-cells

2019 ◽  
Vol 316 (3) ◽  
pp. C434-C443 ◽  
Author(s):  
Toshiaki Sawatani ◽  
Yukiko K. Kaneko ◽  
Isao Doutsu ◽  
Ai Ogawa ◽  
Tomohisa Ishikawa
Keyword(s):  
Insulin Secretion ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Ruthenium Red ◽  
Cell Swelling ◽  
Β Cells ◽  
Β Cell ◽  
Pancreatic Β Cells ◽  
Min6 Cells ◽  
Transient Receptor

β-Cell swelling induces membrane depolarization, which has been suggested to be caused at least partly by the activation of cation channels. Here, we show the identification of the cation channels. In isolated mouse pancreatic β-cells, the exposure to 30% hypotonic solution elicited an increase in cytosolic Ca2+ concentration ([Ca2+]c). The [Ca2+]c elevation was partially inhibited by ruthenium red, a blocker of several Ca2+-permeable channels including transient receptor potential vanilloid receptors [transient receptor potential cation channel subfamily V (TRPV)], and by nicardipine, but not by the depletion of intracellular Ca2+ stores with thapsigargin and caffeine. The hypotonic stimulation also increased insulin secretion from isolated mouse islets, which was significantly suppressed by ruthenium red. Expression of TRPV2 and TRPV4 was confirmed in mouse pancreatic islets and the MIN6 β-cell line by RT-PCR, Western blot, and immunohistochemical analyses. However, neither 4α-phorbol 12,13-didecanoate nor GSK1016790A, TRPV4 activators, showed any apparent effect on [Ca2+]c in isolated mouse β-cells or in MIN6 cells. In contrast, probenecid, a TRPV2 activator, induced an increase in [Ca2+]c in MIN6 cells, which was attenuated by ruthenium red. Moreover, the [Ca2+]c elevation induced by 30% hypotonic stimulation was significantly reduced by knockdown of TRPV2 with siRNA and by tranilast, a TRPV2 inhibitor. The knockdown of TRPV2 also decreased insulin secretion induced by the hypotonic stimulation. In addition, glucose-stimulated insulin secretion was also significantly reduced in the TRPV2-knockdown MIN6 cells. These results suggest that osmotic cell swelling activates TRPV2 in mouse β-cells, thereby causing membrane depolarization and subsequent activation of voltage-dependent Ca2+ channels and insulin secretion.

scholarly journals Molecular Regulations and Functions of the Transient Receptor Potential Channels of the Islets of Langerhans and Insulinoma Cells

Cells ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 685 ◽  
Author(s):  
Md. Shahidul Islam
Keyword(s):  
Insulin Secretion ◽  
Electrical Activity ◽  
Islets Of Langerhans ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Receptor Potential ◽  
Transient Receptor Potential Channels ◽  
Β Cells ◽  
Transient Receptor ◽  
Insulinoma Cells

Insulin secretion from the β-cells of the islets of Langerhans is triggered mainly by nutrients such as glucose, and incretin hormones such as glucagon-like peptide-1 (GLP-1). The mechanisms of the stimulus-secretion coupling involve the participation of the key enzymes that metabolize the nutrients, and numerous ion channels that mediate the electrical activity. Several members of the transient receptor potential (TRP) channels participate in the processes that mediate the electrical activities and Ca2+ oscillations in these cells. Human β-cells express TRPC1, TRPM2, TRPM3, TRPM4, TRPM7, TRPP1, TRPML1, and TRPML3 channels. Some of these channels have been reported to mediate background depolarizing currents, store-operated Ca2+ entry (SOCE), electrical activity, Ca2+ oscillations, gene transcription, cell-death, and insulin secretion in response to stimulation by glucose and GLP1. Different channels of the TRP family are regulated by one or more of the following mechanisms: activation of G protein-coupled receptors, the filling state of the endoplasmic reticulum Ca2+ store, heat, oxidative stress, or some second messengers. This review briefly compiles our current knowledge about the molecular mechanisms of regulations, and functions of the TRP channels in the β-cells, the α-cells, and some insulinoma cell lines.

Inositol lipids and TRPC channel activation

2007 ◽  
Vol 74 ◽  
pp. 37-45 ◽  
Author(s):  
James W. Putney
Keyword(s):  
Plasma Membrane ◽  
Phospholipase C ◽  
Transient Receptor Potential ◽  
Calcium Signalling ◽  
Receptor Potential ◽  
Breakdown Product ◽  
Channel Activation ◽  
Inositol Lipids ◽  
Transient Receptor ◽  
Secondary Mechanism

The original hypothesis put forth by Bob Michell in his seminal 1975 review held that inositol lipid breakdown was involved in the activation of plasma membrane calcium channels or ‘gates’. Subsequently, it was demonstrated that while the interposition of inositol lipid breakdown upstream of calcium signalling was correct, it was predominantly the release of Ca2+ that was activated, through the formation of Ins(1,4,5)P3. Ca2+ entry across the plasma membrane involved a secondary mechanism signalled in an unknown manner by depletion of intracellular Ca2+ stores. In recent years, however, additional non-store-operated mechanisms for Ca2+ entry have emerged. In many instances, these pathways involve homologues of the Drosophila trp (transient receptor potential) gene. In mammalian systems there are seven members of the TRP superfamily, designated TRPC1–TRPC7, which appear to be reasonably close structural and functional homologues of Drosophila TRP. Although these channels can sometimes function as store-operated channels, in the majority of instances they function as channels more directly linked to phospholipase C activity. Three members of this family, TRPC3, 6 and 7, are activated by the phosphoinositide breakdown product, diacylglycerol. Two others, TRPC4 and 5, are also activated as a consequence of phospholipase C activity, although the precise substrate or product molecules involved are still unclear. Thus the TRPCs represent a family of ion channels that are directly activated by inositol lipid breakdown, confirming Bob Michell's original prediction 30 years ago.

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