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: A Short Note On Ca2 %2B Influx

A Short Note On Ca2 %2B Influx Video

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Introduction

In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript. The beating heart possesses the intrinsic ability to adapt cardiac output to changes in mechanical load. The century-old Frank—Starling law and Anrep effect have documented that stretching the heart during diastolic filling increases its contractile force. However, the molecular mechanotransduction mechanism and its impact on cardiac health and disease remain elusive. Piezo1 is pathologically upregulated in both mouse and human diseased hearts via an autonomic response of cardiomyocytes. Thus, Piezo1 serves as a key cardiac mechanotransducer for initiating mechano-chemo transduction and consequently maintaining normal heart function, and might represent a novel therapeutic target for treating human heart diseases. Heart experiences drastic mechanical changes on a beat-to-beat basis and evolves intrinsic mechanisms to adapt cardiac output to hemodynamic conditions 1. Stretching the ventricular wall due to an increase in end-diastolic volume leads to an immediate enhancement of cardiac contraction, followed by a slow response lasting for minutes.

These responses in the intact heart have been respectively described as the Frank—Starling law and the Anrep effect for over years 234which constitute powerful mechanisms to allow the heart to adapt to an abrupt rise in either preload or afterload. However, the molecular identify of the A Short Note On Ca2 %2B Influx mechanotransduction channel and its role in normal and diseased hearts have remained continue reading.

Piezo1 is involved in various aspects of vascular physiology 27including blood and lymphatic vessel development 202128293031vascular tone 23Innfluxarterial remodeling 22and red blood cell volume homeostasis Furthermore, together with its homolog member Piezo2, Piezo1 has been proposed as the mechanosensor in baroreceptor neurons for baroreflex control of blood pressure and heart rate However, the expression and role of Piezo1 in cardiomyocytes and heart function have not been genetically studied. Here, we use mouse genetics and pharmacology to demonstrate the critical role of Piezo1 in cardiac mechano-chemo transduction in normal and diseased hearts.

Previous studies have reported relatively low level of Piezo1 mRNA expression in heart tissues and primarily cultured cardiomyocytes 1226 However, the abundance and localization of Piezo1 proteins in cardiomyocytes have not been systematically characterized. Importantly, the Flag-tagged Piezo1 Piezo1-Flag proteins were specifically detected in the Piezo1-Flag-KI heart tissue either via western blotting of the anti-Flag-immunoprecipitated sample Supplementary Fig.

As a control, heart tissues derived from the wild-type littermate control mice showed no Piezo1-Flag expression Supplementary Fig. Interestingly, %B2 of primarily cultured adult ventricular myocytes using the anti-Flag antibody revealed punctate and striated Oh pattern of the Piezo1-Flag protein specifically in the Piezo1-Flag-KI cells, but not in the control cells Fig.

The endogenous expression of Piezo1 in cardiomyocytes was further confirmed using the previously reported Piezo1-tdTomato knock-in mouse line Piezo1-tdTomato-KI Fig. Immunostaining using the A Short Note On Ca2 %2B Influx antibody clearly detected the expression of the Piezo1-tdTomato proteins in the Piezo1-tdTomato-KI cardiomyocytes, but not in the control cells Fig. In contrast, sarcolemma-localized Piezo1 was not co-localized with the SR-localized type 2 ryanodine receptor RyR2 Fig. Together, these data demonstrate that endogenous Piezo1 proteins are clearly expressed in the sarcolemma of adult cardiomyocytes.

Introduction

The bottom panel shows the enlarged section marked with the yellow box in the middle panel. The near plasma membrane and sarcoplasmic regions are respectively shown in the top and bottom panels. The white arrow on the top panel indicates the sarcolemma region.

Each experiment was repeated independently three times with similar results. Notably, the overexpressed eGFP-Piezo1 proteins showed similar punctate and striated localization patterns as that of Shorf endogenously expressed Piezo1 Fig. In contrast, the expression of Piezo1 in lung, blood vessel, and red blood cells was not affected Fig. Remarkably, the Yoda1 response was nearly completely abolished in cardiomyocytes derived from the Piezo1-KO mice Fig. Experiment was repeated independently three times with similar results. Importantly, such responses were not observed in the Piezo1-KO cardiomyocytes Fig. The peak amplitudes are labeled above the fit.

However, whether mechanosensitive ion channels are involved in the X-ROS signaling has remained unclear. We next directly tested the requirement of Piezo1 for stretch-induced ROS production.

Remarkably, such response was nearly completely abolished in the Piezo1-KO cardiomyocytes Fig. These data provide compelling genetic evidence that Piezo1 mediates both Yoda1- and stretch-induced production of ROS in cardiomyocytes.]