In vivo 31P-MRS assessment of cytosolic [Mg2+] in the human skeletal muscle in different metabolic conditions

Iotti, Stefano; Frassineti, Chiara; Alderighi, Lucia; Sabatini, A.; Vacca, Alberto; Barbiroli, Bruno

doi:10.1016/s0730-725x(00)00132-6

Cited by 62 publications

(61 citation statements)

References 25 publications

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“…Because ischemic episodes are often followed by prolonged hypercontraction without effective relaxation, the Mg 2ϩ -induced increase in the myosin cross-bridge lifetime may play a role in this and other pathological conditions. The free Mg 2ϩ concentrations increase in skeletal muscle during exercise and initial recovery (68), which suggests that Mg 2ϩ could play a role in muscle fatigue. Mg 2ϩ concentrations in the brain were found to vary in different neurological disorders (69) and thus could alter the function of myosin motors, such as myosin V, in neurons.…”

Section: Discussionmentioning

confidence: 99%

Magnesium Modulates Actin Binding and ADP Release in Myosin Motors

Swenson

Trivedi

Rauscher

et al. 2014

Journal of Biological Chemistry

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Background: Magnesium may be an important physiological regulator of myosin motor activity. Results: Mg 2ϩ inhibits the ADP release rate constant in the subset of myosins examined and reduces actin affinity in the post-hydrolysis state in myosin V. Conclusion: Mg 2ϩ alters contractile velocity without altering overall tension-generating capacity. Significance: Mg 2ϩ -dependent regulation of motor activity is conserved in myosin motors.

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Section: Discussionmentioning

confidence: 99%

Magnesium Modulates Actin Binding and ADP Release in Myosin Motors

Swenson

Trivedi

Rauscher

et al. 2014

Journal of Biological Chemistry

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“…In the DM patients, when levels of free Mg 2ϩ were decreased during exercise, ATP was concurrently lowered, but which of these was the primary loss remains uncertain. In the JDM patients, a similar decrease in free Mg 2ϩ during exercise did not result in a further decrease in ATP, indicating that other controlling factors may independently affect ATP and free Mg 2ϩ levels (38,39).…”

Section: Discussionmentioning

confidence: 99%

Magnesium abnormalities of skeletal muscle in dermatomyositis and juvenile dermatomyositis

Niermann

Olsen

Park

2002

Arthritis & Rheumatism

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Objective. To characterize abnormalities in magnesium levels in the muscles of patients with dermatomyositis (DM) and juvenile dermatomyositis (JDM) and to evaluate the beneficial effects of prednisone and immunosuppressive therapy in elevating free magnesium (Mg 2؉ ) and ATP-bound magnesium (Mg-ATP).Methods. The study groups consisted of 12 adult patients with DM and 10 juvenile patients with JDM. The 2 control groups were 11 normal adults and 6 healthy children. Levels of total ATP in the quadriceps muscles of the subjects were determined during rest, exercise, and recovery, using noninvasive P-31 magnetic resonance spectroscopy (MRS). Concentrations of the biologically active free Mg 2؉ and the enzymatically active Mg-ATP complex were determined from the spectroscopy data by calculation of the chemical shifts of the ␤-phosphate peak of ATP.Results. Mg-ATP levels in DM and JDM myopathic muscles were at least 37% lower than those in normal muscles during rest, exercise, and recovery from exercise (P < 0.0005). Free Mg 2؉ levels were normal in DM and JDM myopathic muscles at rest, but were significantly lower than control values during exercise and recovery (P < 0.029 and P < 0.005 for DM and JDM, respectively). Prednisone and immunosuppressive therapy partially reversed the magnesium abnormalities, as evidenced by elevation of the levels of Mg-ATP and free Mg 2؉ .Conclusion. Low levels of Mg-ATP and free Mg 2؉ are concordant with weakness and fatigue observed in DM and JDM patients. Immunosuppressive therapy alleviates, in part, the magnesium deficits in the diseased muscles. Therefore, Mg-ATP and free Mg 2؉ may play a significant role in the pathophysiology of these diseases.Dermatomyositis (DM) and juvenile dermatomyositis (JDM) are similar yet distinct autoimmune diseases characterized by an erythematous rash and severe proximal muscle weakness. The classic diagnoses of DM and JDM are based on the findings of clinical evaluation, elevated serum levels of muscle enzymes, abnormal electromyographic results, and muscle inflammation on biopsy. More recently, magnetic resonance imaging (MRI) and P-31 magnetic resonance spectroscopy (MRS) have been employed as noninvasive techniques for the evaluation of patients with adult and juvenile DM (1-5).MRI has proven to be a reliable indicator of the extent and severity of muscle inflammation. P-31 MRS monitors metabolic status by determining the levels of the high-energy phosphate compounds ATP and phosphocreatine (PCr), which are required for muscle contraction. These compounds are greatly reduced in the affected muscles of patients with DM and JDM (1,4-6). During exercise and recovery, these patients demonstrate inefficient utilization and regeneration of ATP and PCr (1,5,6). Since MRI and MRS are noninvasive procedures with no known side effects, these techniques may be used to quantitatively evaluate the patients' responses to therapy on a longitudinal basis (7).In the present study, we used P-31 MRS to investigate the abnormalities in magnesium levels in the diseas...

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“…Another advantage of using the C-2 peak to measure pH I is the relative insensitivity of its chemical shift to the concentrations of divalent cations (9,11), particularly in light of the fact that intracellular [Mg 2ϩ ] increases during exercise (e.g., Ref. 35). …”

Section: Discussionmentioning

confidence: 99%

The carnosine C‐2 proton's chemical shift reports intracellular pH in oxidative and glycolytic muscle fibers

Damon

Hsu

Stark

et al. 2003

Magnetic Resonance in Med

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The appearance of new peaks in the 7.7-8.6 and 6.8 -7.4 ppm regions of the postexercise 1 H spectrum of frog muscle is reported. These new peaks result from the splitting of single pre-exercise carnosine C-2 and C-4 peaks into two peaks, representing the intracellular pH (pH I ) of oxidative and glycolytic fibers. The following data support this conclusion: 1) comparison of means and regression analysis indicates equivalence of the pH I measurements by 1 H and 31 P NMR; 2) the pre-and poststimulation concentrations of carnosine are equal; 3) in ischemic rat hindlimb muscles, the presence of a single, more acidic peak in the plantaris; a single, less acidic peak in the soleus; and two peaks (more and less acidic) in the gastrocnemius correspond to published values for the fiber-type composition of these muscles; and 4) in muscles treated with iodoacetate prior to and during stimulation, a second peak never appears. These data indicate that it is feasible to measure separately the pH I of oxidative and glycolytic fibers using 1 H NMR spectroscopy. Measuring intracellular pH (pH I ) is important in studies of many cellular processes. In studies of muscle metabolism and exercise, it is desirable to measure separately the pH I of oxidative and glycolytic fibers. pH I measurements are commonly made using 31 P NMR spectroscopy, using the inorganic phosphate (P i ) peak's chemical shift. Following intense muscle exercise, the single pre-exercise P i peak frequently splits into two or more poststimulation P i peaks (P i,A and P i,B ), which are believed to correspond to P i in glycolytic and oxidative fibers, respectively (1-7). However, because of the low NMR sensitivity of the phosphorus nucleus, it is sometimes not possible to distinguish a P i peak from noise when the concentration of P i is low. Extreme broadening of the P i peak during exercise has also been observed (5), interfering with the ability to resolve individual peaks.The C-2 and C-4 protons on the imidazole ring of carnosine (␤-alanyl histidine) have pK A 's of approximately 7.0 and chemical shifts that are sensitive to pH in the physiological range, providing an alternative means of measuring pH noninvasively (8). Several authors have taken advantage of this pH sensitivity to measure the pH I of muscle in vivo and ex vivo (8 -13), and of muscle extracts (8,14). Specific applications have been made to muscle in resting (8,10,11,(13)(14)(15)(16), diseased (16), caffeinetreated (14), and exercised (9,11,12) states. Pan et al. (11) and Hitzig et al. (13) found high correlations between pH I measurements by the C-2 and P i methods.While studying exercising ex vivo frog gastrocnemii, we also observed the C-2 peak of carnosine at ϳ8.0 ppm prior to stimulation. However, we noted two peaks (one at ϳ8.53 and one at ϳ8.37 ppm) following exercise. In this study, we tested the hypothesis that they both originate from C-2 protons of carnosine. We also tested the hypothesis that the downfield peak (which we call carnosine C-2 A ) originates from a more acidic compartm...

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In vivo 31P-MRS assessment of cytosolic [Mg2+] in the human skeletal muscle in different metabolic conditions

Cited by 62 publications

References 25 publications

Magnesium Modulates Actin Binding and ADP Release in Myosin Motors

Magnesium Modulates Actin Binding and ADP Release in Myosin Motors

Magnesium abnormalities of skeletal muscle in dermatomyositis and juvenile dermatomyositis

The carnosine C‐2 proton's chemical shift reports intracellular pH in oxidative and glycolytic muscle fibers

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