Genetic manipulation of calcium-handling proteins in cardiac myocytes. II. Mathematical modeling studies

American Journal of Physiology. Heart and Circulatory Physiology
Pierre Coutu, Joseph M Metzger

Abstract

We developed a mathematical model specific to rat ventricular myocytes that includes electrophysiological representation, ionic homeostasis, force production, and sarcomere movement. We used this model to interpret, analyze, and compare two genetic manipulations that have been shown to increase myocyte relaxation rates, parvalbumin (Parv) de novo expression, and sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA2a) overexpression. The model was used to seek mechanistic insights into 1) the relative contribution of two mechanisms by which SERCA2a overexpression modifies Ca2+ sequestration, i.e., more pumps and an increase in the SERCA2a-to-phospholamban ratio, 2) the mechanisms behind postrest potentiation and how Parv and SERCA2a influence this response, and 3) why Parv myocytes retain their fast kinetics when endogenous SERCA2a is partially impaired by thapsigargin (a condition used to mimic diastolic dysfunction). The model was also utilized to predict whether Parv metal-binding characteristics might be modified to improve diastolic and systolic functions and whether Parv or SERCA2a might affect diastolic Ca2+ levels and myocyte energetics. One outcome of the model was to demonstrate a higher peak and total ATP consumption in ...Continue Reading

References

Jan 1, 1991·Annual Review of Medicine·B H Lorell
May 1, 1996·Journal of Molecular and Cellular Cardiology·J A Negroni, E C Lascano
Sep 2, 1998·The American Journal of Physiology·A J BakerS A Camacho
Jul 17, 1999·The American Journal of Physiology·H M HimmelU Ravens
May 17, 2000·The Journal of Clinical Investigation·K R Chien
May 17, 2000·The Journal of Clinical Investigation·R PassierE N Olson
Sep 12, 2000·Current Cardiology Reports·P P DzejaA Terzic
Nov 23, 2000·The Journal of Biological Chemistry·T R ShannonD M Bers
Aug 22, 2001·American Journal of Physiology. Heart and Circulatory Physiology·S I YasudaH Sugi
May 3, 2002·Clinical and Experimental Pharmacology & Physiology·Jianyi Zhang
Oct 5, 2002·Circulation Research·Thomas R ShannonDonald M Bers
Oct 22, 2002·American Journal of Physiology. Heart and Circulatory Physiology·Babar ChaudhriSian E Harding
Jan 2, 2003·The Journal of Physiology·Federica del Monte, Roger J Hajjar
Feb 15, 2003·Trends in Cardiovascular Medicine·Pierre CoutuJoseph M Metzger
Dec 9, 2003·The Journal of Physiology·Renée Ventura-ClapierVladimir Veksler
Aug 28, 2004·American Journal of Physiology. Heart and Circulatory Physiology·Pierre Coutu, Joseph M Metzger

❮ Previous
Next ❯

Citations

Oct 9, 2012·American Journal of Physiology. Heart and Circulatory Physiology·S A NiedererN P Smith
May 12, 2016·Biophysical Journal·Michelle L AspJoseph M Metzger
May 7, 2008·Cell Biochemistry and Biophysics·Wang Wang, Joseph M Metzger
Apr 5, 2012·The Journal of Physiology·Denis NoblePenelope J Noble
Aug 5, 2017·The Journal of Physiological Sciences : JPS·Yuttamol MuangkramAkira Amano

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.