The TRPC3/6/7 subfamily of cation channels

Trebak, Mohamed; Vázquez, Guillermo; Bird, Gary S.; Putney, James W.

doi:10.1016/s0143-4160(03)00056-3

Cited by 205 publications

(195 citation statements)

References 82 publications

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“…Most importantly, we show that TRPC3 forms a heteromeric complex with TRPC6 and the Ca 2ϩ -signaling proteins, G␣ q/11 , PLC␤1 and ␤3, and IP 3 R-1 and -3. In aggregate, these data suggest that apically localized TRPC channels can be regulated by Ca 2ϩ -signaling mechanisms, as proposed previously for these channels (10,14,21).…”

Section: Discussionsupporting

confidence: 85%

“…1 The abbreviations used are: PLC, phospholipase C; IP 3 The TRPC subfamily of ion channel proteins form Ca 2ϩ -permeable cation channels that are activated by agonist stimulation of PIP 2 hydrolysis (12,13). TRPC3, -6, and -7 form agonist-regulated channels that can also be directly activated by DAG (14), whereas TRPC1 and TRPC4 appear to form store-operated channels in some cell types (15)(16)(17). Furthermore, a number of the TRPC proteins, e.g.…”

mentioning

confidence: 99%

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Apical Localization of a Functional TRPC3/TRPC6-Ca2+-Signaling Complex in Polarized Epithelial Cells

Bandyopadhyay

Swaim

Liu

et al. 2005

Journal of Biological Chemistry

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Section: Discussionsupporting

confidence: 85%

mentioning

confidence: 99%

Apical Localization of a Functional TRPC3/TRPC6-Ca2+-Signaling Complex in Polarized Epithelial Cells

Bandyopadhyay

Swaim

Liu

et al. 2005

Journal of Biological Chemistry

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“…The basal channel activity of TRPC6 is tightly regulated (39). In contrast, TRPC3 and TRPC7 have considerable constitutive activity when expressed in various cell lines (46). Despite the low basal activity of TRPC6 channels, results from transgenic mice with cardiomyocyte-specific expression of TRPC3 or TRPC6 channels show that the up-regulation of TRPC6 channel proteins is essential for the development of cardiac hypertrophy (13,14).…”

Section: Discussionmentioning

confidence: 99%

Phosphorylation of TRPC6 Channels at Thr69 Is Required for Anti-hypertrophic Effects of Phosphodiesterase 5 Inhibition

Nishida

Watanabe

Sato

et al. 2010

Journal of Biological Chemistry

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Activation of Ca2؉ signaling induced by receptor stimulation and mechanical stress plays a critical role in the development of cardiac hypertrophy. A canonical transient receptor potential protein subfamily member, TRPC6, which is activated by diacylglycerol and mechanical stretch, works as an upstream regulator of the Ca 2؉ signaling pathway. Although activation of protein kinase G (PKG) inhibits TRPC6 channel activity and cardiac hypertrophy, respectively, it is unclear whether PKG suppresses cardiac hypertrophy through inhibition of TRPC6. Here, we show that inhibition of cGMP-selective PDE5 (phosphodiesterase 5) suppresses endothelin-1-, diacylglycerol analog-, and mechanical stretch-induced hypertrophy through inhibition of Ca 2؉ influx in rat neonatal cardiomyocytes. influx. Substitution of Ala for Thr 69 in TRPC6 abolished the anti-hypertrophic effects of PDE5 inhibition. In addition, chronic PDE5 inhibition by oral sildenafil treatment actually induced TRPC6 phosphorylation in mouse hearts. Knockdown of RGS2 (regulator of G protein signaling 2) and RGS4, both of which are activated by PKG to reduce G␣ q -mediated signaling, did not affect the suppression of receptor-activated Ca 2؉ influx by PDE5 inhibition. These results suggest that phosphorylation and functional suppression of TRPC6 underlie prevention of pathological hypertrophy by PDE5 inhibition.Pathological hypertrophy of the heart, induced by pressure overload, such as chronic hypertension and aortic stenosis, is a major risk factor for heart failure and cardiovascular mortality (1). Neurohumoral factors, such as norepinephrine, angiotensin II (Ang II), 2 and endothelin-1 (ET-1), and mechanical stress are believed to be prominent contributors for pressure overloadinduced cardiac hypertrophy (2, (9). A partial depolarization of plasma membrane by receptor stimulation is reported to increase the frequency of Ca 2ϩ oscillations, leading to activation of nuclear factor of activated T cells (NFAT), a transcription factor that is predominantly regulated by calcineurin (10). Recent reports have indicated that transient receptor potential canonical (TRPC) subfamily proteins play an essential role in agonistinduced membrane depolarization (11, 12). The relevance of TRPC channels to pathological hypertrophy is underscored by the observations that heart-targeted transgenic mice expressing TRPC channels caused hypertrophy (13,14) and that TRPC proteins were up-regulated in hypertrophied and failing hearts (14 -17). Among seven TRPC subfamilies, increased channel activities of TRPC1, TRPC3, and TRPC6 have been implicated in cardiac hypertrophy in vivo. TRPC1 is known to function not * This study was supported by grants from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (to M. Nishida, M. Nakaya, and H. Kurose), a grant-in-aid for scientific research on Innovative Areas (to M. Nishida), a grant-in-aid for scientific research on Priority Areas (H. Kurose), and grants from the Naito Foundation, the Nakatomi Foundation, the Sapporo ...

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“…TRPC3, a member of the transient receptor potential family of ion channels, has been shown to be activated by agonist activation of plasma membrane G-protein-coupled receptors, by synthetic diacylglycerols, and by depletion of intracellular Ca 2+ stores in some cell types [28][29][30].…”

Section: Trpc3mentioning

confidence: 99%

Vascular Responses to Shear Stress: The Involvement of Mechanosensors in Endothelial Cells

Ngai¹

2012

TOCVJ

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Shear stress, the frictional drag on the endothelium from blood flow, is a major determinant of vascular physiology and pathology. Due to the pulsatile nature of blood flow, blood vessels are subjected to significant variations in mechanical forces. Endothelial cells situated at the interface between blood and the vessel wall play a crucial role in detecting and responding to the mechanical forces generated by shear stress. Multiple sensing mechanisms are used by endothelial cells to detect changes in mechanical forces, leading to the activation of signaling networks. This review attempts to bring together recent findings on the mechanosensors present in the endothelial cells, and the regulation of endothelium-derived vasoactive autacoid production by shear stress.

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The TRPC3/6/7 subfamily of cation channels

Cited by 205 publications

References 82 publications

Apical Localization of a Functional TRPC3/TRPC6-Ca2+-Signaling Complex in Polarized Epithelial Cells

Apical Localization of a Functional TRPC3/TRPC6-Ca2+-Signaling Complex in Polarized Epithelial Cells

Phosphorylation of TRPC6 Channels at Thr69 Is Required for Anti-hypertrophic Effects of Phosphodiesterase 5 Inhibition

Vascular Responses to Shear Stress: The Involvement of Mechanosensors in Endothelial Cells

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