			Home About us Contact

Contraction Coupling (contraction + coupling)

Distribution by Scientific Domains

Medical Sciences	66%
Life Sciences	33%

Selected Abstracts

Role Of Protein Kinase C In Myogenic Calcium, Contraction Coupling Of Rat Cannulated Mesenteric Small Arteries

CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 10 2001
Jos Pm Wesselman
SUMMARY 1. The present study was designed to determine the role of protein kinase C (PKC) in the myogenic response of small arteries. In particular, we tested whether inhibition of PKC reverses the previously found pressure-induced elevation of contractile element calcium sensitivity. 2. Rat mesenteric small arteries were cannulated and pressurized. The internal diameter was continuously monitored with a video camera and intracellular calcium levels were measured by means of fura-2. Myogenic responses were observed when the pressure was raised stepwise from 20 to 60 and then to 100 mmHg in physiological saline solution and during application of phenylephrine (0.1 or 1 ,mol/L) or potassium (36 mmol/L). 3. The PKC inhibitors H-7 (20 ,mol/L), staurosporine (100 nmol/L) and calphostin C (10 nmol/L) all completely abolished the myogenic response. Whereas staurosporine caused an ongoing reduction in intracellular calcium, pressure-induced calcium transients were not affected by either H-7 or calphostin C. In particular, the slope of the wall tension,calcium relationship remained similar in the presence of both H-7 and calphostin C, despite an upward shift of this relationship to higher calcium levels in the case of calphostin C. 4. These results show that activity of PKC isoform(s) is essential for myogenic calcium,contraction coupling. [source]

Excitation,Contraction Coupling In Skeletal Muscle: Comparisons With Cardiac Muscle

CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 3 2000
Gd Lamb
SUMMARY 1. The present review describes the mechanisms involved in controlling Ca2+ release from the sarcoplasmic reticulum (SR) of skeletal muscle, which ultimately regulates contraction. 2. Comparisons are made between cardiac and skeletal muscle with respect to: (i) the role of the dihydropyridine receptors (DHPR) as Ca2+ channels and voltage-sensors; (ii) the regulation of the ryanodine receptor (RyR)/Ca2+ -release channels in the SR; and (iii) the importance of Ca2+ -induced Ca2+ release. 3. It is shown that the key differences of the skeletal muscle Ca2+ -release channel (RyR1), namely the increase in its stimulation by ATP and its inhibition by Mg2+, are critical for its direct regulation by the associated DHPR and, consequently, for the fast, accurate control of skeletal muscle contraction. [source]

Mutations in RYR1 in malignant hyperthermia and central core disease,

HUMAN MUTATION, Issue 10 2006
Rachel Robinson
Abstract The RYR1 gene encodes the skeletal muscle isoform ryanodine receptor and is fundamental to the process of excitation,contraction coupling and skeletal muscle calcium homeostasis. Mapping to chromosome 19q13.2, the gene comprises 106 exons and encodes a protein of 5,038 amino acids. Mutations in the gene have been found in association with several diseases: the pharmacogenetic disorder, malignant hyperthermia (MH); and three congenital myopathies, including central core disease (CCD), multiminicore disease (MmD), and in an isolated case of a congenital myopathy characterized on histology by cores and rods. The majority of gene mutations reported are missense changes identified in cases of MH and CCD. In vitro analysis has confirmed that alteration of normal calcium homeostasis is a functional consequence of some of these changes. Genotype,phenotype correlation studies performed using data from MH and CCD patients have also suggested that mutations may be associated with a range of disease severity phenotypes. This review aims to summarize the current understanding of RYR1 mutations reported in association with MH and CCD and the present viewpoint on the use of mutation data to aid clinical diagnosis of these conditions. Hum Mutat 27(10), 977,989, 2006. © 2006 Wiley-Liss, Inc. [source]

Effects of Wall Stress on the Dynamics of Ventricular Fibrillation: A Simulation Study Using a Dynamic Mechanoelectric Model of Ventricular Tissue

JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 7 2008
SATOKO HIRABAYASHI master of environment
Introduction: To investigate the mechanisms underlying the increased prevalence of ventricular fibrillation (VF) in the mechanically compromised heart, we developed a fully coupled electromechanical model of the human ventricular myocardium. Methods and Results: The model formulated the biophysics of specific ionic currents, excitation,contraction coupling, anisotropic nonlinear deformation of the myocardium, and mechanoelectric feedback (MEF) through stretch-activated channels. Our model suggests that sustained stretches shorten the action potential duration (APD) and flatten the electrical restitution curve, whereas stretches applied at the wavefront prolong the APD. Using this model, we examined the effects of mechanical stresses on the dynamics of spiral reentry. The strain distribution during spiral reentry was complex, and a high strain-gradient region was located in the core of the spiral wave. The wavefront around the core was highly stretched, even at lower pressures, resulting in prolongation of the APD and extension of the refractory area in the wavetail. As the left ventricular pressure increased, the stretched area became wider and the refractory area was further extended. The extended refractory area in the wavetail facilitated the wave breakup and meandering of tips through interactions between the wavefront and wavetail. Conclusions: This simulation study indicates that mechanical loading promotes meandering and wave breaks of spiral reentry through MEF. Mechanical loading under pathological conditions may contribute to the maintenance of VF through these mechanisms. [source]

Remodelling of action potential and intracellular calcium cycling dynamics during subacute myocardial infarction promotes ventricular arrhythmias in Langendorff-perfused rabbit hearts

THE JOURNAL OF PHYSIOLOGY, Issue 3 2007
Chung-Chuan Chou
We hypothesize that remodelling of action potential and intracellular calcium (Cai) dynamics in the peri-infarct zone contributes to ventricular arrhythmogenesis in the postmyocardial infarction setting. To test this hypothesis, we performed simultaneous optical mapping of Cai and membrane potential (Vm) in the left ventricle in 15 rabbit hearts with myocardial infarction for 1 week. Ventricular premature beats frequently originated from the peri-infarct zone, and 37% showed elevation of Cai prior to Vm depolarization, suggesting reverse excitation,contraction coupling as their aetiology. During electrically induced ventricular fibrillation, the highest dominant frequency was in the peri-infarct zone in 61 of 70 episodes. The site of highest dominant frequency had steeper action potential duration restitution and was more susceptible to pacing-induced Cai alternans than sites remote from infarct. Wavebreaks during ventricular fibrillation tended to occur at sites of persistently elevated Cai. Infusion of propranolol flattened action potential duration restitution, reduced wavebreaks and converted ventricular fibrillation to ventricular tachycardia. We conclude that in the subacute phase of myocardial infarction, the peri-infarct zone exhibits regions with steep action potential duration restitution slope and unstable Cai dynamics. These changes may promote ventricular extrasystoles and increase the incidence of wavebreaks during ventricular fibrillation. Whereas increased tissue heterogeneity after subacute myocardial infarction creates a highly arrhythmogenic substrate, dynamic action potential and Cai cycling remodelling also contribute to the initiation and maintenance of ventricular fibrillation in this setting. [source]

Disruption of excitation,contraction coupling and titin by endogenous Ca2+ -activated proteases in toad muscle fibres

THE JOURNAL OF PHYSIOLOGY, Issue 3 2005
Esther Verburg
This study investigated the effects of elevated, physiological levels of intracellular free [Ca2+] on depolarization-induced force responses, and on passive and active force production by the contractile apparatus in mechanically skinned fibres of toad iliofibularis muscle. Excitation,contraction (EC) coupling was retained after skinning and force responses could be elicited by depolarization of the transverse-tubular (T-) system. Raising the cytoplasmic [Ca2+] to ,1 ,m or above for 3 min caused an irreversible reduction in the depolarization-induced force response by interrupting the coupling between the voltage sensors in the T-system and the Ca2+ release channels in the sarcoplasmic reticulum. This uncoupling showed a steep [Ca2+] dependency, with 50% uncoupling at ,1.9 ,m Ca2+. The uncoupling occurring with 2 ,m Ca2+ was largely prevented by the calpain inhibitor leupeptin (1 mm). Raising the cytoplasmic [Ca2+] above 1 ,m also caused an irreversible decline in passive force production in stretched skinned fibres in a manner graded by [Ca2+], though at a much slower relative rate than loss of coupling. The progressive loss of passive force could be rapidly stopped by lowering [Ca2+] to 10 nm, and was almost completely inhibited by 1 mm leupeptin but not by 10 ,m calpastatin. Muscle homogenates preactivated by Ca2+ exposure also evidently contained a diffusible factor that caused damage to passive force production in a Ca2+ -dependent manner. Western blotting showed that: (a) calpain-3 was present in the skinned fibres and was activated by the Ca2+exposure, and (b) the Ca2+ exposure in stretched skinned fibres resulted in proteolysis of titin. We conclude that the disruption of EC coupling occurring at elevated levels of [Ca2+] is likely to be caused at least in part by Ca2+ -activated proteases, most likely by calpain-3, though a role of calpain-1 is not excluded. [source]

Effects of Formaldehyde on Cardiovascular System in In Situ Rat Hearts

BASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 4 2009
Daisuke Takeshita
After 20,30 min. of intravenous infusion of 3.7% formaldehyde solution (FA) at 10 ,l (3.7 mg)/kg/min, normal and hypertrophic hearts showed significant decreases in left ventricle end-systolic pressure (ESP), heart rate and cardiac output per minute, indicating an acute pumping failure. Hypertrophic hearts showed significantly smaller ESP, stroke volumes and cardiac output than those in normal hearts. Systolic pressure,volume area at midrange left ventricular volume (PVAmLVV: a mechanical work capability index) was significantly smaller than that in normal hearts and per cent of mean PVAmLVVversus pre-infusion mean value in hypertrophic hearts was significantly decreased compared to normal hearts 30 min. after FA infusion. The marked decrease in pH, base excess and no changes in PaO2 and PaCO2 suggest metabolic acidosis. The correction of metabolic acidosis with 9% NaHCO3 did not influence on the acute pumping failure, indicating that metabolic acidosis did not cause it. Ultrastructural observations revealed marked dilation of the sarcoplasmic reticulum with intact sarcolemmal membranes and no disintegration of muscle myofibrils. Ryanodine receptors and calcium (Ca2+) pumps (SERCA2A) located in the sarcoplasmic reticulum have major roles in the cytosolic Ca2+ handling. Taken together, acute pumping failure by FA may derive from the impairment of Ca2+ handling in the cardiac excitation,contraction coupling. [source]

EXCITATION,CONTRACTION COUPLING FROM THE 1950s INTO THE NEW MILLENNIUM

CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 9 2006
AF Dulhunty
SUMMARY 1Excitation,contraction coupling is broadly defined as the process linking the action potential to contraction in striated muscle or, more narrowly, as the process coupling surface membrane depolarization to Ca2+ release from the sarcoplasmic reticulum. 2We now know that excitation,contraction coupling depends on a macromolecular protein complex or ,calcium release unit'. The complex extends the extracellular space within the transverse tubule invaginations of the surface membrane, across the transverse tubule membrane into the cytoplasm and then across the sarcoplasmic reticulum membrane and into the lumen of the sarcoplasmic reticulum. 3The central element of the macromolecular complex is the ryanodine receptor calcium release channel in the sarcoplasmic reticulum membrane. The ryanodine receptor has recruited a surface membrane L-type calcium channel as a ,voltage sensor' to detect the action potential and the calcium-binding protein calsequestrin to detect in the environment within the sarcoplasmic reticulum. Consequently, the calcium release channel is able to respond to surface depolarization in a manner that depends on the Ca2+ load within the calcium store. 4The molecular components of the ,calcium release unit' are the same in skeletal and cardiac muscle. However, the mechanism of excitation,contraction coupling is different. The signal from the voltage sensor to ryanodine receptor is chemical in the heart, depending on an influx of external Ca2+ through the surface calcium channel. In contrast, conformational coupling links the voltage sensor and the ryanodine receptor in skeletal muscle. 5Our current understanding of this amazingly efficient molecular signal transduction machine has evolved over the past 50 years. None of the proteins had been identified in the 1950s; indeed, there was debate about whether the molecules involved were, in fact, protein. Nevertheless, a multitude of questions about the molecular interactions and structures of the proteins and their interaction sites remain to be answered and provide a challenge for the next 50 years. [source]