Track topics on Twitter Track topics that are important to you
Cardiac contractility increases as sarcomere length increases, suggesting that intrinsic molecular mechanisms underlie the Frank-Starling relationship to confer increased cardiac output with greater ventricular filling. Myosin's capacity to bind with actin and generate force in a muscle cell is Ca(2+)-regulated by thin-filament proteins and spatially-regulated by sarcomere length as thick-to-thin filament overlap varies. One mechanism underlying greater cardiac contractility as sarcomere length increases could involve longer myosin attachment time (ton) due to slowed myosin kinetics at longer sarcomere length. To test this idea, we used stochastic length-perturbation analysis in skinned rat papillary muscle strips to measure ton as [MgATP] varied (0.05-5 mM) at 1.9 and 2.2 µm sarcomere lengths. From this ton-MgATP relationship, we calculated cross-bridge MgADP release rate and MgATP binding rates. As MgATP increased, t_on decreased for both sarcomere lengths, but ton was roughly 70% longer for 2.2 vs. 1.9 µm sarcomere length at maximally-activated conditions. These ton differences were driven by a slower MgADP release rate at 2.2 µm sarcomere length (41±3 vs. 74±7 s(-1)), as MgATP binding rate was not different between the two sarcomere lengths. At sub-maximal activation levels near the pCa50 value of the tension-pCa relationship for each sarcomere length, length-dependent increases in ton were roughly 15% longer for 2.2 vs. 1.9 µm sarcomere length. These changes in cross-bridge kinetics could amplify cooperative cross-bridge contributions to force production and thin-filament activation at longer sarcomere length, and suggest that length-dependent changes in myosin MgADP release rate may contribute to the Frank-Starling relationship in the heart.
This article was published in the following journal.
Name: American journal of physiology. Heart and circulatory physiology
During spermatogenesis, interconnected haploid spermatids segregate undesired cellular contents into residual bodies (RBs) before detaching from RBs. It is unclear how this differentiation process is ...
The length of stay among psychiatric in-patients is usually longer than that of others. In-patient management is costly and longer length of stay can lead to catastrophic costs. We conducted this stud...
Myosins are a large family of actin filament-based motor proteins with a broad range of functions such as intracellular membrane trafficking, endocytosis, exocytosis, organellar transport, growth cone...
Myosin is a hexameric contractile protein composed of 2 heavy chains associated with 4 light chains of 2 distinct classes - 2 regulatory light chains (MYL2) and 2 essential light chains (MYL3). The my...
It has been reported that donor age affects patient outcomes after liver transplantation, and that telomere length is associated with age. However, to our knowledge, the impact of donor age and donor ...
The primary objectives of this study are (i) to select an oral modified release (MR) formulation and dose of omecamtiv mecarbil for chronic twice daily (BID) dosing in subjects with HF and...
Limb length inequality is when a person has one leg that is longer than the other. This research will look at correcting limb length inequality in adults with knee or hip symptoms. This s...
This study is a Phase 1, randomized, open label, single dose, 6 treatment, 6 period, 6 sequence study in healthy adult volunteers. A total of 24 (4 in each treatment sequence) healthy male...
The purpose of this study is to test the following hypotheses: 1. Enteral glutamine administration decreases in-hospital mortality in adult subjects with severe thermal burn injuri...
Neuraxial anaesthesia can be more difficult and associated with more complications if the patient's bony landmarks are difficult to palpate. They are more likely to be difficult to palpate...
A subclass of myosin found in ACANTHAMOEBA. It is a non-filamentous myosin containing a single 180-kDa myosin heavy chain.
Parts of the myosin molecule resulting from cleavage by proteolytic enzymes (PAPAIN; TRYPSIN; or CHYMOTRYPSIN) at well-localized regions. Study of these isolated fragments helps to delineate the functional roles of different parts of myosin. Two of the most common subfragments are myosin S-1 and myosin S-2. S-1 contains the heads of the heavy chains plus the light chains and S-2 contains part of the double-stranded, alpha-helical, heavy chain tail (myosin rod).
The subfamily of myosin proteins that are commonly found in muscle fibers. Myosin II is also involved a diverse array of cellular functions including cell division, transport within the GOLGI APPARATUS, and maintaining MICROVILLI structure.
A subclass of myosin involved in organelle transport and membrane targeting. It is abundantly found in nervous tissue and neurosecretory cells. The heavy chains of myosin V contain unusually long neck domains that are believed to aid in translocating molecules over large distances.
An enzyme that phosphorylates myosin light chains in the presence of ATP to yield myosin-light chain phosphate and ADP, and requires calcium and CALMODULIN. The 20-kDa light chain is phosphorylated more rapidly than any other acceptor, but light chains from other myosins and myosin itself can act as acceptors. The enzyme plays a central role in the regulation of smooth muscle contraction.
Arthritis Fibromyalgia Gout Lupus Rheumatic Rheumatology is the medical specialty concerned with the diagnosis and management of disease involving joints, tendons, muscles, ligaments and associated structures (Oxford Medical Diction...
Cardiovascular disease (CVD)
Acute Coronary Syndromes (ACS) Blood Cardiovascular Dialysis Hypertension Stent Stroke Vascular Cardiovascular disease (CVD) includes all the diseases of the heart and circulation including coronary heart disease (angina...