scholarly journals Astrocyte regulation of cerebral vascular tone

2013 ◽  
Vol 305 (5) ◽  
pp. H609-H619 ◽  
Author(s):  
Jessica A. Filosa ◽  
Jennifer A. Iddings
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Vascular Tone ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Transient Receptor Potential Channel ◽  
Cellular Mechanisms ◽  
Wide Range ◽  
Transient Receptor ◽  
Regulation Of Vascular Tone

Cerebral blood flow is controlled by two crucial processes, cerebral autoregulation (CA) and neurovascular coupling (NVC) or functional hyperemia. Whereas CA ensures constant blood flow over a wide range of systemic pressures, NVC ensures rapid spatial and temporal increases in cerebral blood flow in response to neuronal activation. The focus of this review is to discuss the cellular mechanisms by which astrocytes contribute to the regulation of vascular tone in terms of their participation in NVC and, to a lesser extent, CA. We discuss evidence for the various signaling modalities by which astrocytic activation leads to vasodilation and vasoconstriction of parenchymal arterioles. Moreover, we provide a rationale for the contribution of astrocytes to pressure-induced increases in vascular tone via the vasoconstrictor 20-HETE (a downstream metabolite of arachidonic acid). Along these lines, we highlight the importance of the transient receptor potential channel of the vanilloid family (TRPV4) as a key molecular determinant in the regulation of vascular tone in cerebral arterioles. Finally, we discuss current advances in the technical tools available to study NVC mechanisms in the brain as it relates to the participation of astrocytes.

scholarly journals Regulation of the transient receptor potential channel TRPM3 by phosphoinositides

2015 ◽  
Vol 146 (1) ◽  
pp. 51-63 ◽  
Author(s):  
Balázs I. Tóth ◽  
Maik Konrad ◽  
Debapriya Ghosh ◽  
Florian Mohr ◽  
Christian R. Halaszovich ◽  
...  
Keyword(s):  
Acetylcholine Receptors ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Transient Receptor Potential Channel ◽  
Membrane Receptors ◽  
Muscarinic Acetylcholine Receptors ◽  
Cellular Mechanisms ◽  
Dynamic Regulation ◽  
Transient Receptor ◽  
Phosphatidylinositol Phosphates

The transient receptor potential (TRP) channel TRPM3 is a calcium-permeable cation channel activated by heat and by the neurosteroid pregnenolone sulfate (PregS). TRPM3 is highly expressed in sensory neurons, where it plays a key role in heat sensing and inflammatory hyperalgesia, and in pancreatic β cells, where its activation enhances glucose-induced insulin release. However, despite its functional importance, little is known about the cellular mechanisms that regulate TRPM3 activity. Here, we provide evidence for a dynamic regulation of TRPM3 by membrane phosphatidylinositol phosphates (PIPs). Phosphatidylinositol 4,5-bisphosphate (PI[4,5]P2) and ATP applied to the intracellular side of excised membrane patches promote recovery of TRPM3 from desensitization. The stimulatory effect of cytosolic ATP on TRPM3 reflects activation of phosphatidylinositol kinases (PI-Ks), leading to resynthesis of PIPs in the plasma membrane. Various PIPs directly enhance TRPM3 activity in cell-free inside-out patches, with a potency order PI(3,4,5)P3 > PI(3,5)P2 > PI(4,5)P2 ≈ PI(3,4)P2 >> PI(4)P. Conversely, TRPM3 activity is rapidly and reversibly inhibited by activation of phosphatases that remove the 5-phosphate from PIPs. Finally, we show that recombinant TRPM3, as well as the endogenous TRPM3 in insuloma cells, is rapidly and reversibly inhibited by activation of phospholipase C–coupled muscarinic acetylcholine receptors. Our results reveal basic cellular mechanisms whereby membrane receptors can regulate TRPM3 activity.

Abstract 11605: Proteinase-Activated Receptor-2 is Responsible for Amplified Function of Transient Receptor Potential Channel A1 in Skeletal Muscle Sensory Neurons of Rats With Peripheral Artery Disease

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Jihong Xing ◽  
Jian Lu ◽  
Jianhua Li
Keyword(s):  
Skeletal Muscle ◽  
Blood Flow ◽  
Peripheral Artery Disease ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Transient Receptor Potential Channel ◽  
Peripheral Artery ◽  
Drg Neurons ◽  
Artery Disease ◽  
Transient Receptor

Background: Limb ischemia occurs in peripheral artery disease (PAD). Sympathetic nerve activity that regulates blood flow directed to the limbs is augmented during exercise in this disease and transient receptor potential channel A1 (TRPA1) in thin-fiber muscle afferents contributes to the amplified sympathetic responses. The objective of this study was to determine the role played by proteinase-activated receptor-2 (PAR2) in regulating abnormal TRPA1 function. Methods: A rat model of femoral artery ligation was employed to study PAD. Dorsal root ganglion (DRG) tissues of control limbs and limbs with 24 hours of femoral occlusion were obtained to examine the protein levels of PAR2 using western blot analysis. Also, current responses induced by activation of TRPA1 in skeletal muscle DRG neurons of control limbs and ligated limbs were characterized using whole-cell patch clamp methods. All data are presented as mean ± SE. Results: Femoral occlusion significantly increased expression of PAR2 in DRG (optical density: 1.06±0.03 in control vs. 1.45±0.04 after occlusion, P< 0.05; n = 6 in each group). In addition, femoral occlusion amplified the amplitude of DRG current responses evoked by stimulation of TRPA1 with AITC (a TRPA1 agonist, 100 μM). The peak amplitude of TRPA1 currents was 0.28±0.03 nA in control and 0.41±0.04 nA ( P< 0.05 vs. control; n = 12 in each group) after occlusion, respectively. Activation of PAR2 with SL-NH2 (a PAR2 agonist, 100 μM) increased the TRPA1 currents by 78±10% in DRG neurons of control limb and by 125±10% in DRG neurons of ligated limb ( P< 0.05 vs. control; n = 8 in each group). Moreover, the potentiating effects of PAR2 activation were significantly inhibited by application of phospholipase C (PLC) inhibitors or phosphatidylinositol-4,5-bisphosphate (PIP2). Conclusions: A functional interaction in PAR2 and TRPA1 in muscle sensory nerves likely contributes to the amplified sympathetic responsiveness observed in PAD and that the PLC/PIP2 is engaged in sensitization mechanism of TRPA1. These findings provide a pathophysiological basis for autonomic responses during exercise activity in this disease, which may further help to aim at a potential therapeutic approach for improvement of blood flow in PAD patients.

scholarly journals Function of the Porcine TRPC1 Gene in Myogenesis and Muscle Growth

Cells ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 147
Author(s):  
Yu Fu ◽  
Peng Shang ◽  
Bo Zhang ◽  
Xiaolong Tian ◽  
Ruixue Nie ◽  
...  
Keyword(s):  
Transient Receptor Potential ◽  
Growth Traits ◽  
Expression Profiles ◽  
Muscle Growth ◽  
Receptor Potential ◽  
Transient Receptor Potential Channel ◽  
Nucleotide Polymorphisms ◽  
Pig Breeds ◽  
Muscle Tissues ◽  
Transient Receptor

In animals, muscle growth is a quantitative trait controlled by multiple genes. Previously, we showed that the transient receptor potential channel 1 (TRPC1) gene was differentially expressed in muscle tissues between pig breeds with divergent growth traits base on RNA-seq. Here, we characterized TRPC1 expression profiles in different tissues and pig breeds and showed that TRPC1 was highly expressed in the muscle. We found two single nucleotide polymorphisms (SNPs) (C-1763T and C-1604T) in TRPC1 that could affect the promoter region activity and regulate pig growth rate. Functionally, we used RNAi and overexpression to illustrate that TRPC1 promotes myoblast proliferation, migration, differentiation, fusion, and muscle hypertrophy while inhibiting muscle degradation. These processes may be mediated by the activation of Wnt signaling pathways. Altogether, our results revealed that TRPC1 might promote muscle growth and development and plays a key role in Wnt-mediated myogenesis.

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