scholarly journals Pregnancy-enhanced store-operated Ca2+ channel function in uterine artery endothelial cells is associated with enhanced agonist-specific transient receptor potential channel 3-inositol 1,4,5-trisphosphate receptor 2 interaction

2006 ◽  
Vol 190 (2) ◽  
pp. 385-395 ◽  
Author(s):  
Shannon M Gifford ◽  
Fu-Xian Yi ◽  
Ian M Bird
Keyword(s):  
Endothelial Cells ◽  
Uterine Artery ◽  
Transient Receptor Potential ◽  
Purinergic Receptor ◽  
Receptor Potential ◽  
Cell Types ◽  
Transient Receptor Potential Channels ◽  
Significant Difference ◽  
Transient Receptor ◽  
Trisphosphate Receptor

We have previously shown that endothelial cells (EC) derived from the uterine artery (UA) of both pregnant (P-UAEC) and nonpregnant (NP-UAEC) ewes show a biphasic intracellular free Ca2+ ([Ca2+]i) response after ATP stimulation. In each case, the initial transient peak, caused by the release of Ca2+ from the intracellular Ca2+ stores, is mediated by purinergic receptor-Y2 and is very similar in both cell types. However, the sustained phase in particular, caused by the influx of extracellular Ca2+, is heightened in the P-UAEC, and associates with an increased ability of the cells to demonstrate enhanced capacitative Ca2+ entry (CCE) via store-operated channels (SOCs). Herein we demonstrated that the difference in the sustained [Ca2+]i response is maintained for at least 30 min. When 2-aminoethoxydiphenyl borate (2APB) (an inhibitor of the inosital 1,4,5-trisphosphate receptor (IP3R) and possibly SOC) was used in conjunction with ATP, it was capable of completely inhibiting CCE. Since 2APB can inhibit SOC in some cell types and 2APB was capable of inhibiting CCE in the UAEC model, the role of SOC in CCE was first evaluated using the classical inhibitor La3+. The ATP-induced sustained phase was inhibited by 10 μM La3+, implying a role for SOC in the [Ca2+]i response. Since canonical transient receptor potential channels (TRPCs) have recently been identified as putative SOCs in many cell types, including EC, the expression levels of several isoforms were evaluated in UAEC. Expression of TRPC3 and TRPC6 channels in particular was detected, but no significant difference in expression level was found between NP- and P-UAEC. Nonetheless, we were able to show that IP3R2 interacts with TRPC3 in UAEC, forming a protein complex, and that this interaction is considerably enhanced in an agonist sensitive manner by pregnancy. Thus, while IP3R and TRPC isoforms are not altered in their expression by pregnancy, enhanced functional interaction of TRPC3 with IP3R2 may underlie pregnancy-enhanced CCE in the UAEC model and so explain the prolonged [Ca2+]i sustained phase seen in response to ATP.

Expression and relative abundance of short transient receptor potential channels in the rat renal microcirculation

2004 ◽  
Vol 286 (3) ◽  
pp. F546-F551 ◽  
Author(s):  
Carie S. Facemire ◽  
Peter J. Mohler ◽  
William J. Arendshorst
Keyword(s):  
Relative Abundance ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Cell Types ◽  
Calcium Entry ◽  
Transient Receptor Potential Channels ◽  
Trpc Channels ◽  
Renal Microcirculation ◽  
Resistance Vessels ◽  
Transient Receptor

In the resistance vessels of the renal microcirculation, store- and/or receptor-operated calcium entry contribute to the rise in vascular smooth muscle cell (VSMC) intracellular calcium concentration in response to vasoconstrictor hormones. Short transient receptor potential (TRPC) channels are widely expressed in mammalian tissues and are proposed mediators of voltage-independent cation entry in multiple cell types, including VSMCs. The seven members of the TRPC gene family (TRPC1-7) encode subunit proteins that are thought to form homo- and heterotetrameric channels that are differentially regulated depending on their subunit composition. In the present study, we demonstrate the relative abundance of TRPC mRNA and protein in freshly isolated rat renal resistance vessels, glomeruli, and aorta. TRPC1, 3, 4, 5, and 6 mRNA and protein were detected in both renal resistance vessels and aorta, whereas TRPC2 and TRPC7 mRNA were not expressed. TRPC1, 3, 5, and 6 protein was present in glomeruli. TRPC3 and TRPC6 protein levels were significantly greater in the renal resistance vessels, about six- to eightfold higher than in aorta. These data suggest that TRPC3 and TRPC6 may play a role in mediating voltage-independent calcium entry in renal resistance vessels that is functionally distinct from that in aorta.

scholarly journals Pregnancy-enhanced Ca2+ responses to ATP in uterine artery endothelial cells is due to greater capacitative Ca2+ entry rather than altered receptor coupling

2006 ◽  
Vol 190 (2) ◽  
pp. 373-384 ◽  
Author(s):  
Shannon M Gifford ◽  
Fu-Xian Yi ◽  
Ian M Bird
Keyword(s):  
Endothelial Cells ◽  
Uterine Artery ◽  
Purinergic Receptor ◽  
Cell Types ◽  
P2y Receptors ◽  
Receptor Expression ◽  
Receptor Subtype ◽  
Initial Transient ◽  
Receptor Coupling ◽  
Specific Variation

Uterine artery endothelial cells (UAEC) derived from pregnant (P-UAEC) and nonpregnant (NP-UAEC) ewes retain pregnancy-specific differences in cell signaling as well as vasodilator production through passage 4. In particular, when P- and NP-UAEC are stimulated with ATP over a 2.5 min recording period, they exhibit similar initial transient peaks in the intracellular free Ca2+ concentration ([Ca2+]i), but the P-UAEC show a heightened sustained phase. In order to establish whether thiswas due to an altered subclass of purinergic receptor (P2), both the dose dependencyof [Ca2+]i responses to ADP and UTP and the profile of purinergic receptor expression are determined in NP- and P-UAEC. Our findings indicate that while several isoforms of P2X and P2Y receptors are present, it is P2Y2 that is responsible for the ATP-induced initial transient peak in both cell types. We also characterized several key components of the ATP-induced Ca2+ signaling cascade, including the inositol 1,4,5-trisphosphate receptor and G-proteins, but could not confirm any pregnancy-specific variation in the protein expression that correlated with pregnancy-specific differences in prolonged Ca2+ signaling. We thus investigated whether such a difference may be inherent to the cell itself rather than specific to the purinergic receptor-signaling pathway. Using thapsigargin (Tg), we were able to demonstrate that the initial Tg-sensitive intracellular pool of Ca2+is nearly identical with the capacity in both cell types, but the P-UAEC is nonetheless capable of greater capacitative Ca2+ entry (CCE) than NP-UAEC. Furthermore, CCE induced by Tg could be dramatically inhibited by 2-aminoethoxydiphenyl borate, suggesting a role for store-operated channels in the ATP-induced [Ca2+]i response. We conclude that changes at the level of capacitative entry mechanisms rather than switching of receptor subtype or coupling to phospholipase C underlies pregnancy adaptation of UAEC at the level of Ca2+signaling.

scholarly journals Effects of Ginger and its Pungent Constituents on Transient Receptor Potential Channels

2017 ◽  
Vol 112 (3) ◽  
pp. 250a
Author(s):  
Young-Soo Kim ◽  
Chan Sik Hong ◽  
Sang Weon Lee ◽  
Joo Hyun Nam ◽  
Byung Joo Kim
Keyword(s):  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Transient Receptor Potential Channels ◽  
Potential Channels ◽  
Transient Receptor

What Evolutionary Evidence Implies About the Identity of the Mechanoelectrical Couplers in Vascular Smooth Muscle Cells

Physiology ◽  
2021 ◽  
Vol 36 (5) ◽  
pp. 292-306
Author(s):  
Heather A. Drummond
Keyword(s):  
Transient Receptor Potential ◽  
Molecular Model ◽  
Receptor Potential ◽  
Transient Receptor Potential Channels ◽  
Potential Channels ◽  
Transient Receptor ◽  
Paradigm Shifting ◽  
G Protein Coupled ◽  
Evolutionary Role

Loss of pressure-induced vasoconstriction increases susceptibility to renal and cerebral vascular injury. Favored paradigms underlying initiation of the response include transient receptor potential channels coupled to G protein-coupled receptors or integrins as transducers. Degenerin channels may also mediate the response. This review addresses the 1) evolutionary role of these molecules in mechanosensing, 2) limitations to identifying mechanosensitive molecules, and 3) paradigm shifting molecular model for a VSMC mechanosensor.

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