Intracellular [Ca2+]i homeostasis is essential for normal cardiac function and integrity, and dysregulation of [Ca2+]i is a hallmark of advanced heart failure.2 The primary trigger for cardiac [Ca2+]i transients is calcium entry through the pore subunit of the voltage-dependent L-type channels (L-VDCC), but their role in heart failure is still controversial. Electrophysiological studies on individual L-VDCCs from failing human heart have revealed an increased single-channel activity but the mechanism for this biophysical phenotype has remained unknown.3,4
In a paper in this week’s PLoS ONE, Roger Hullin of the Swiss Heart Center Bern, Jan Matthes of University of Cologne, Germany, and collaborators in both Germany and the USA demonstrate an up-regulation of expression of an accessory subunit of the L-VDCC complex (beta 2-subunit) that is responsible for the altered channel behavior in human heart failure. Similar changes of both beta 2-subunit expression and single-channel behavior were also observed in a mouse model of heart failure with cardiac overexpression of the human L-type Ca2+-channel pore. The causal role of the increased beta 2-subunit expression for the “heart failure type” of single L-VDCC characteristics was proven when the authors developed a novel, cardiac-specific, drug-inducible beta 2a subunit overexpression transgenic mouse which was crossbred with the channel pore overexpressing mouse when still nonfailing (“Adaptive phase”). In the nonfailing double transgenics, the induction of beta 2a protein expression increased the activity of single ventricular L-VDCC, rendering these channels phenotypically identical to human and mouse heart failure.
The authors conclude that electrical remodeling of the L-VDCC, based on gene expression changes, is an early step in a cascade ultimately induced in heart failure. This provides a rational framework for novel therapeutic intervention in heart failure.
4.Bodi I et al. (2005) The L-type calcium channel in the heart: the beat goes on. J Clin Invest 115: 3306-17.
Climate Impact Research in Hannover: Small Plants against Large Waves
17.08.2018 | Leibniz Universität Hannover
First transcription atlas of all wheat genes expands prospects for research and cultivation
17.08.2018 | Leibniz-Institut für Pflanzengenetik und Kulturpflanzenforschung
New design tool automatically creates nanostructure 3D-print templates for user-given colors
Scientists present work at prestigious SIGGRAPH conference
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Scientists at the University of California, Los Angeles present new research on a curious cosmic phenomenon known as "whistlers" -- very low frequency packets...
Scientists develop first tool to use machine learning methods to compute flow around interactively designable 3D objects. Tool will be presented at this year’s prestigious SIGGRAPH conference.
When engineers or designers want to test the aerodynamic properties of the newly designed shape of a car, airplane, or other object, they would normally model...
Researchers from TU Graz and their industry partners have unveiled a world first: the prototype of a robot-controlled, high-speed combined charging system (CCS) for electric vehicles that enables series charging of cars in various parking positions.
Global demand for electric vehicles is forecast to rise sharply: by 2025, the number of new vehicle registrations is expected to reach 25 million per year....
Proteins must be folded correctly to fulfill their molecular functions in cells. Molecular assistants called chaperones help proteins exploit their inbuilt folding potential and reach the correct three-dimensional structure. Researchers at the Max Planck Institute of Biochemistry (MPIB) have demonstrated that actin, the most abundant protein in higher developed cells, does not have the inbuilt potential to fold and instead requires special assistance to fold into its active state. The chaperone TRiC uses a previously undescribed mechanism to perform actin folding. The study was recently published in the journal Cell.
Actin is the most abundant protein in highly developed cells and has diverse functions in processes like cell stabilization, cell division and muscle...
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