Clinical science (London, England : 1979) | VOL. 136
Read

Diminished Rbfox1 increases vascular constriction by dynamically regulating alternative splicing of CaV1.2 calcium channel in hypertension.

Publication Date Jun 17, 2022

Abstract

Calcium influx from depolarized CaV1.2 calcium channels triggers the contraction of vascular smooth muscle cells (VSMCs), which is important for maintaining vascular myogenic tone and blood pressure. The function of CaV1.2 channel can be subtly modulated by alternative splicing (AS), and its aberrant splicing involves in the pathogenesis of multiple cardiovascular diseases. The RNA-binding protein Rbfox1 is reported to regulate the AS events of CaV1.2 channel in the neuronal development, but its potential roles in vascular CaV1.2 channels and vasoconstriction remain undefined. Here, we detect Rbfox1 is expressed in rat vascular smooth muscles. Moreover, the protein level of Rbfox1 is dramatically decreased in the hypertensive small arteries from spontaneously hypertensive rats in comparison with normotensive ones from Wistar-Kyoto rats. In VSMCs, Rbfox1 could dynamically regulate the AS of CaV1.2 exons 9* and 33. By whole-cell patch clamp, we identify knockdown of Rbfox1 induces the hyperpolarization of CaV1.2 current-voltage relationship curve in VSMCs. Furthermore, siRNA-mediated knockdown of Rbfox1 increases the K+-induced constriction of rat mesenteric arteries. In summary, our results indicate Rbfox1 modulates vascular constriction by dynamically regulating CaV1.2 alternative exons 9* and 33. Therefore, our work elucidates the underlying mechanisms for CaV1.2 channels regulation and provides a potential therapeutic target for hypertension.

Concepts

Vascular Smooth Muscle Cells Alternative Splicing Function Of CaV1 Rat Vascular Smooth Muscles Vascular CaV1 Normotensive Ones Patch Clamp Contraction Of Smooth Muscle Cells Alternative Exons Wistar-Kyoto Rats

Round-ups are the summaries of handpicked papers around trending topics published every week. These would enable you to scan through a collection of papers and decide if the paper is relevant to you before actually investing time into reading it.

Coronavirus Research Articles published between Nov 28, 2022 to Dec 04, 2022

R DiscoveryDec 05, 2022
R DiscoveryArticles Included:  5

The coronavirus disease 2019 (COVID-19) is a contagious disease that is caused by a novel coronavirus. Bentham is offering subject-based scholarly con...

Read More

Climate change Research Articles published between Nov 28, 2022 to Dec 04, 2022

R DiscoveryDec 05, 2022
R DiscoveryArticles Included:  5

We use cookies to improve your website experience. To learn about our use of cookies and how you can manage your cookie settings, please see our Cooki...

Read More

Quality Of Education Research Articles published between Nov 28, 2022 to Dec 04, 2022

R DiscoveryDec 05, 2022
R DiscoveryArticles Included:  4

Introduction: The Internet is an extensively used source of medical education by the public. YouTube is a valuable source of information which can be ...

Read More

Gender Equality Research Articles published between Nov 28, 2022 to Dec 04, 2022

R DiscoveryDec 05, 2022
R DiscoveryArticles Included:  3

Gender equity in the classroom is important for teachers to think about in order to ensure they are creating safe environments that allow their studen...

Read More

Coronavirus Pandemic

You can also read COVID related content on R COVID-19

R ProductsCOVID-19

ONE PROBLEM . ONE PURPOSE . ONE PLACE

Creating the world’s largest AI-driven & human-curated collection of research, news, expert recommendations and educational resources on COVID-19

COVID-19 Dashboard

Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on “as is” basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The Copyright Law.