Regulation of phosphorylase kinase by low concentrations of Ca ions upon muscle contraction: the connection between metabolism and muscle contraction and the connection between muscle physiology and Ca-dependent signal transduction

It had long been one of the crucial questions in muscle physiology how glycogenolysis is regulated in connection with muscle contraction, when we found the answer to this question in the last half of the 1960s. By that time, the two principal currents of muscle physiology, namely, the metabolic flow starting from glycogen and the mechanisms of muscle contraction, had already been clarified at the molecular level thanks to our senior researchers. Thus, the final question we had to answer was how to connect these two currents. We found that low concentrations of Ca ions (10−7–10−4 M) released from the sarcoplasmic reticulum for the regulation of muscle contraction simultaneously reversibly activate phosphorylase kinase, the enzyme regulating glycogenolysis. Moreover, we found that adenosine 3′,5′-monophosphate (cyclic AMP), which is already known to activate muscle phosphorylase kinase, is not effective in the absence of such concentrations of Ca ions. Thus, cyclic AMP is not effective by itself alone and only modifies the activation process in the presence of Ca ions (at that time, cyclic AMP-dependent protein kinase had not yet been identified). After a while, it turned out that our works have not only provided the solution to the above problem on muscle physiology, but have also been considered as the first report of Ca-dependent protein phosphorylation, which is one of the central problems in current cell biology. Phosphorylase kinase is the first protein kinase to phosphorylate a protein resulting in the change in the function of the phosphorylated protein, as shown by Krebs and Fischer. Our works further showed that this protein kinase is regulated in a Ca-dependent manner. Accordingly, our works introduced the concept of low concentrations of Ca ions, which were first identified as the regulatory substance of muscle contraction, to the vast field of Ca biology including signal transduction

Actions of Calcium on Smooth Muscle a

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72185/1/j.1749-6632.1988.tb33358.x.pd

Cardiac biomarkers of acute coronary syndrome: from history to high-sensitivity cardiac troponin

The role of cardiac troponins as diagnostic biomarkers of myocardial injury in the context of acute coronary syndrome (ACS) is well established. Since the initial 1st-generation assays, 5th-generation high-sensitivity cardiac troponin (hs-cTn) assays have been developed, and are now widely used. However, its clinical adoption preceded guidelines and even best practice evidence. This review summarizes the history of cardiac biomarkers with particular emphasis on hs-cTn. We aim to provide insights into using hs-cTn as a quantitative marker of cardiomyocyte injury to help in the differential diagnosis of coronary versus non-coronary cardiac diseases. We also review the recent evidence and guidelines of using hs-cTn in suspected ACS

A model of open-loop control of equilibrium position and stiffness of the human elbow joint

According to the equilibrium point theory, the control of posture and movement involves the setting of equilibrium joint positions (EP) and the independent modulation of stiffness. One model of EP control, the α-model, posits that stable EPs and stiffness are set open-loop, i.e. without the aid of feedback. The purpose of the present study was to explore for the elbow joint the range over which stable EPs can be set open-loop and to investigate the effect of co-contraction on intrinsic low-frequency elbow joint stiffness (

Progress in muscular dystrophy research with special emphasis on gene therapy

Duchenne muscular dystrophy (DMD) is an X-linked, progressive muscle-wasting disease caused by mutations in the DMD gene. Since the disease was described by physicians in the 19th century, information about the subject has been accumulated. One author (Sugita) was one of the coworkers who first reported that the serum creatine kinase (CK) level is elevated in progressive muscular dystrophy patients. Even 50 years after that first report, an elevated serum CK level is still the most useful marker in the diagnosis of DMD, a sensitive index of the state of skeletal muscle, and useful to evaluate therapeutic effects. In the latter half of this article, we describe recent progress in the therapy of DMD, with an emphasis on gene therapies, particularly exon skipping

Effects of hypoxia on the distribution of calcium in arterial smooth muscle cells of rats and swine

Exposure to hypoxia caused an increase in the hematocrit and right heart weight of experimental rats, but did not affect calcium-45 uptake by pulmonary arterial smooth muscle cells. However, autoradiographic studies showed that hypoxia apparently caused a shift of 45-Ca from primarily extracellular sites in arteries of control rats to intracellular sites in tissues of hypertensive rats. Cytochemical studies of calcium distributions in pulmonary arterial smooth muscle cells support the autoradiographic data and show that in both rats and swine the majority of pyroantimonate granules occur extracellularly in control tissues. In contrast, hypoxic tissues displayed a greatly reduced number of granules in extracellular sites and an increase in the amount of precipitate in intracellular sites. In pulmonary arterial smooth muscle cells from hypoxic rats most of the precipitate was associated with the caveolae intracellulares, while in corresponding cells from hypoxic swine the majority of the pyroantimonate granules were localized to the sarcoplasmic reticulum. Hypoxia may produce pulmonary hypertension by interfering with the ability of the arterial smooth muscle cells to maintain transmembrane ionic gradients, thus producing an effective increase in cytoplasmic calcium levels. The increased calcium may then activate the contractile apparatus to produce a sustained vasoconstriction.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47664/1/441_2004_Article_BF00223235.pd