English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

MicroRNAs are small endogenous noncoding RNAs that regulate protein expression by hybridization to imprecise complementary sequences of target mRNAs. Changes in abundance of muscle-specific microRNA,miR-1 , have been implicated in cardiac disease, including arrhythmia and heart failure. However, the specific molecular targets and cellular mechanisms involved in the action ofmiR-1 in the heart are only beginning to emerge. In this study we investigated the effects of increased expression ofmiR-1 on excitation–contraction coupling and Ca2+ cycling in rat ventricular myocytes using methods of electrophysiology, Ca2+ imaging and quantitative immunoblotting. Adenoviral-mediated overexpression ofmiR-1 in myocytes resulted in a marked increase in the amplitude of the inward Ca2+ current, flattening of Ca2+ transients voltage dependence, and enhanced frequency of spontaneous Ca2+ sparks while reducing the sarcoplasmic reticulum Ca2+ content as compared with control. In the presence of isoproterenol, rhythmically paced,miR-1 –overexpressing myocytes exhibited spontaneous arrhythmogenic oscillations of intracellular Ca2+ , events that occurred rarely in control myocytes under the same conditions. The effects ofmiR-1 were completely reversed by the CaMKII inhibitor KN93. Although phosphorylation of phospholamban was not altered,miR-1 overexpression increased phosphorylation of the ryanodine receptor (RyR2) at S2814 (Ca2+ /calmodulin-dependent protein kinase) but not at S2808 (protein kinase A). Overexpression ofmiR-1 was accompanied by a selective decrease in expression of the protein phosphatase PP2A regulatory subunit B56α involved in PP2A targeting to specialized subcellular domains. We conclude thatmiR-1 enhances cardiac excitation–contraction coupling by selectively increasing phosphorylation of the L-type and RyR2 channels via disrupting localization of PP2A activity to these channels.

circulation research

<i>miR-1</i> Overexpression Enhances Ca <sup>2+</sup> Release and Promotes Cardiac Arrhythmogenesis by Targeting PP2A Regulatory Subunit B56α and Causing CaMKII-Dependent Hyperphosphorylation of RyR2

miR-1 Overexpression Enhances Ca 2+ Release and Promotes Cardiac Arrhythmogenesis by Targeting PP2A Regulatory Subunit B56α and Causing CaMKII-Dependent Hyperphosphorylation of RyR2

miR-1 Overexpression Enhances Ca ²⁺ Release and Promotes Cardiac Arrhythmogenesis by Targeting PP2A Regulatory Subunit B56α and Causing CaMKII-Dependent Hyperphosphorylation of RyR2