Canonical Transient Receptor Potential Channels and Vascular Smooth Muscle Cell Plasticity

Nishida, Motohiro; Tanaka, Tomohiro; Mangmool, Supachoke; Nishiyama, Kazuhiro; Nishimura, Akiyoshi

doi:10.12997/jla.2020.9.1.124

Cited by 17 publications

(10 citation statements)

References 109 publications

(133 reference statements)

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“…We revealed a positive link between βAR and α 1 AR through TRPC6-mediated Zn 2+ influx. TRPC channels are thought to play a fundamental role in the amplification of G q PCR signaling pathways 53 . We suggest that TRPC6 enhances G s protein-coupled βAR signaling in rodent hearts through Zn 2+ influx.…”

Section: Discussionmentioning

confidence: 99%

Myocardial TRPC6-mediated Zn2+ influx induces beneficial positive inotropy through β-adrenoceptors

et al. 2022

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Baroreflex control of cardiac contraction (positive inotropy) through sympathetic nerve activation is important for cardiocirculatory homeostasis. Transient receptor potential canonical subfamily (TRPC) channels are responsible for α1-adrenoceptor (α1AR)-stimulated cation entry and their upregulation is associated with pathological cardiac remodeling. Whether TRPC channels participate in physiological pump functions remains unclear. We demonstrate that TRPC6-specific Zn2+ influx potentiates β-adrenoceptor (βAR)-stimulated positive inotropy in rodent cardiomyocytes. Deletion of trpc6 impairs sympathetic nerve–activated positive inotropy but not chronotropy in mice. TRPC6-mediated Zn2+ influx boosts α1AR-stimulated βAR/Gs-dependent signaling in rat cardiomyocytes by inhibiting β-arrestin-mediated βAR internalization. Replacing two TRPC6-specific amino acids in the pore region with TRPC3 residues diminishes the α1AR-stimulated Zn2+ influx and positive inotropic response. Pharmacological enhancement of TRPC6-mediated Zn2+ influx prevents chronic heart failure progression in mice. Our data demonstrate that TRPC6-mediated Zn2+ influx with α1AR stimulation enhances baroreflex-induced positive inotropy, which may be a new therapeutic strategy for chronic heart failure.

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Section: Discussionmentioning

confidence: 99%

Myocardial TRPC6-mediated Zn2+ influx induces beneficial positive inotropy through β-adrenoceptors

et al. 2022

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“…RNA Isolation and Quantitative Real-Time RT PCR Total RNA was extracted and complementary DNA was synthesized as previously described. 15) Quantitative real-time PCR was performed as previously described. 15) Primer sequences used are summarized in supplementary Table 1.…”

Section: Methodsmentioning

confidence: 99%

“…15) Quantitative real-time PCR was performed as previously described. 15) Primer sequences used are summarized in supplementary Table 1. In order to normalize cDNA levels, 18s ribosomal RNA (rRNA) expression was used as an endogenous control.…”

Section: Methodsmentioning

confidence: 99%

Deletion of TRPC3 or TRPC6 Fails to Attenuate the Formation of Inflammation and Fibrosis in Non-alcoholic Steatohepatitis

Nishiyama

Toyama

Kato

et al. 2021

Biological & Pharmaceutical Bulletin

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Non-alcoholic steatohepatitis (NASH) is a disease that has progressed from non-alcoholic fatty liver disease (NAFLD) and is characterized by inflammation and fibrosis. Two transient receptor potential canonical (TRPC) subfamily members, TRPC3 and TRPC6 (TRPC3/6), reportedly participate in the development of fibrosis in cardiovascular and renal systems. We hypothesized that TRPC3/6 may also participate in NASH fibrosis. We evaluated the effects of TRPC3 or TRPC6 functional deficiency in a NASH mouse model using choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD). Wild-type (WT) and TRPC3 or TRPC6 gene-deficient (KO) mice were fed with CDAHFD or standard diet for 6 weeks. The CDAHFD-induced body weight loss in TRPC6 KO mice was significantly lower compared with WT mice with CDAHFD. CDAHFD treatment significantly increased TRPC3 mRNA expression level and tissue weight in WT liver, which were suppressed in TRPC3 KO mice. However, either systemic deletion of TRPC3 or TRPC6 failed to attenuate liver steatosis, inflammation and fibrosis. These results imply that TRPC3 and TRPC6 are unlikely to be involved in liver dysfunction and fibrosis of NASH model mice.

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“…Notably, the vascular response to direct smooth muscle vasodilators is unaffected by ischemic stroke, suggesting that dysfunction in other cell types in cerebral vessels accounts for the impaired neurovascular coupling [ 86 ]. However, TRPC6 has been implicated in VSMC phenotype switching under ischemic conditions [ 87 , 88 ]. TRPC6, along with other TRP channels subfamilies, are expressed in pericytes [ 89 ].…”

Section: Neurovascular Coupling In Ischemic Strokementioning

confidence: 99%

Novel Mechanistic Insights and Potential Therapeutic Impact of TRPC6 in Neurovascular Coupling and Ischemic Stroke

Shekhar

Liu

Wang

et al. 2021

IJMS

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Ischemic stroke is one of the most disabling diseases and a leading cause of death globally. Despite advances in medical care, the global burden of stroke continues to grow, as no effective treatments to limit or reverse ischemic injury to the brain are available. However, recent preclinical findings have revealed the potential role of transient receptor potential cation 6 (TRPC6) channels as endogenous protectors of neuronal tissue. Activating TRPC6 in various cerebral ischemia models has been found to prevent neuronal death, whereas blocking TRPC6 enhances sensitivity to ischemia. Evidence has shown that Ca2+ influx through TRPC6 activates the cAMP (adenosine 3’,5’-cyclic monophosphate) response element-binding protein (CREB), an important transcription factor linked to neuronal survival. Additionally, TRPC6 activation may counter excitotoxic damage resulting from glutamate release by attenuating the activity of N-methyl-D-aspartate (NMDA) receptors of neurons by posttranslational means. Unresolved though, are the roles of TRPC6 channels in non-neuronal cells, such as astrocytes and endothelial cells. Moreover, TRPC6 channels may have detrimental effects on the blood–brain barrier, although their exact role in neurovascular coupling requires further investigation. This review discusses evidence-based cell-specific aspects of TRPC6 in the brain to assess the potential targets for ischemic stroke management.

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Canonical Transient Receptor Potential Channels and Vascular Smooth Muscle Cell Plasticity

Cited by 17 publications

References 109 publications

Myocardial TRPC6-mediated Zn2+ influx induces beneficial positive inotropy through β-adrenoceptors

Myocardial TRPC6-mediated Zn2+ influx induces beneficial positive inotropy through β-adrenoceptors

Deletion of TRPC3 or TRPC6 Fails to Attenuate the Formation of Inflammation and Fibrosis in Non-alcoholic Steatohepatitis

Novel Mechanistic Insights and Potential Therapeutic Impact of TRPC6 in Neurovascular Coupling and Ischemic Stroke

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