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Objective: To investigate the effects and mechanisms of miRNA 221 on myocardial ischemia/reperfusion injury (MIRI) in mice through the regulation of phospholamban (PLB) expression.

Methods: The MIRI mouse model was created and mice were divided into sham, MIRI, MIRI+ 221, and MIRI+ scr groups, with miRNA 221 overexpression induced in the myocardium of MIRI mice by targeted myocardial injection. Quantitative RT-PCR analysis was performed to observe the variation in miRNA 221, PLB, SERCA2, RYR2, NCX1, Cyt C and caspase 3 mRNA levels in myocardium, while Western blot assessed the levels of PLB, p-PLB (Ser16), p-PLB (Thr17), SERCA2, RYR2, NCX1, Cyt C and caspase 3 proteins.

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Inactivation of CaV1 and CaV2 channels.

J Gen Physiol

March 2025

Department of Physiology, University of Maryland School of Medicine, Baltimore, MD, USA.

Voltage-gated Ca2+ channels (VGCCs) are highly expressed throughout numerous biological systems and play critical roles in synaptic transmission, cardiac excitation, and muscle contraction. To perform these various functions, VGCCs are highly regulated. Inactivation comprises a critical mechanism controlling the entry of Ca2+ through these channels and constitutes an important means to regulate cellular excitability, shape action potentials, control intracellular Ca2+ levels, and contribute to long-term potentiation and depression.

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Reactive oxygen species (ROS) produced by NADPH oxidase promote contraction of peripheral arteries, which is especially pronounced in early postnatal period in comparison to adulthood, but the mechanisms of such vasomotor influence are poorly understood. We tested the hypothesis that Rho-kinase and protein kinase C (PKC) mediate procontractile influence of NADPH oxidase derived ROS in peripheral artery of early postnatal rats. In addition, we evaluated the involvement Src-kinase and L-type voltage-gated Ca channels (LTCC) into procontractile influence of ROS, produced by NADPH oxidase, because of their known interplay with Rho-kinase and PKC pathways.

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Background: Rho-associated kinases 1 and 2 (ROCK1 and ROCK2) regulate critical cell functions, including actomyosin contractility, apoptosis, and proliferation. Some studies suggest that ROCK inhibition may serve as a treatment for liver fibrosis. More investigation is needed to understand the role of hepatocyte ROCK signaling in vivo, especially in the context of profibrotic liver injury.

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Muscle development and maintenance is central to the normal functioning of animals. Muscle tissues exhibit high levels of activity and require the dynamic turnover of proteins. An actomyosin scaffold functions with additional proteins comprising the basic contractile subunit of striated muscle, known as the sarcomere.

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