scholarly journals Inward Flux of Lactate- through Monocarboxylate Transporters Contributes to Regulatory Volume Increase in Mouse Muscle Fibres

PLoS ONE ◽  
2013 ◽  
Vol 8 (12) ◽  
pp. e84451 ◽  
Author(s):  
Michael I. Lindinger ◽  
Matthew J. Leung ◽  
Thomas J. Hawke
Keyword(s):  
Monocarboxylate Transporters ◽  
Muscle Fibres ◽  
Mouse Muscle ◽  
Volume Increase ◽  
Regulatory Volume Increase

scholarly journals Hypertonic stress increases the Na+ conductance of rat hepatocytes in primary culture.

1995 ◽  
Vol 105 (4) ◽  
pp. 507-535 ◽  
Author(s):  
F Wehner ◽  
H Sauer ◽  
R K Kinne
Keyword(s):  
Cell Membrane ◽  
Primary Culture ◽  
Regulatory Volume Decrease ◽  
Rat Hepatocytes ◽  
Laser Scanning Microscopy ◽  
Specific Cell ◽  
Volume Increase ◽  
Regulatory Volume Increase ◽  
Hypertonic Stress ◽  
Cell Volumes

We studied the ionic mechanisms underlying the regulatory volume increase of rat hepatocytes in primary culture by use of confocal laser scanning microscopy, conventional and ion-sensitive microelectrodes, cable analysis, microfluorometry, and measurements of 86Rb+ uptake. Increasing osmolarity from 300 to 400 mosm/liter by addition of sucrose decreased cell volumes to 88.6% within 1 min; thereafter, cell volumes increased to 94.1% of control within 10 min, equivalent to a regulatory volume increase (RVI) by 44.5%. This RVI was paralleled by a decrease in cell input resistance and in specific cell membrane resistance to 88 and 60%, respectively. Ion substitution experiments (high K+, low Na+, low Cl-) revealed that these membrane effects are due to an increase in hepatocyte Na+ conductance. During RVI, ouabain-sensitive 86Rb+ uptake was augmented to 141% of control, and cell Na+ and cell K+ increased to 148 and 180%, respectively. The RVI, the increases in Na+ conductance and cell Na+, as well as the activation of Na+/K(+)-ATPase were completely blocked by 10(-5) mol/liter amiloride. At this concentration, amiloride had no effect on osmotically induced cell alkalinization via Na+/H+ exchange. When osmolarity was increased from 220 to 300 mosm/liter (by readdition of sucrose after a preperiod of 15 min in which the cells underwent a regulatory volume decrease, RVD) cell volumes initially decreased to 81.5%; thereafter cell volumes increased to 90.8% of control. This post-RVD-RVI of 55.0% is also mediated by an increase in Na+ conductance. We conclude that rat hepatocytes in confluent primary culture are capable of RVI as well as of post-RVD-RVI. In this system, hypertonic stress leads to a considerable increase in cell membrane Na+ conductance. In concert with conductive Na+ influx, cell K+ is then increased via activation of Na+/K(+)-ATPase. An additional role of Na+/H+ exchange in the volume regulation of rat hepatocytes remains to be defined.

Secondary regulatory volume increase conferred on Xenopus oocytes by expression of AE2 anion exchanger

1997 ◽  
Vol 272 (1) ◽  
pp. C191-C202 ◽  
Author(s):  
L. Jiang ◽  
M. N. Chernova ◽  
S. L. Alper
Keyword(s):  
Volume Regulation ◽  
Xenopus Oocytes ◽  
Disulfonic Acid ◽  
Functional Coupling ◽  
Intrinsic Volume ◽  
Volume Increase ◽  
Regulatory Volume Increase ◽  
Hypertonic Stimulation ◽  
Shrinkage Prior ◽  
Hypotonic Swelling

Xenopus oocytes lack volume regulation and Cl/anion-exchange (AE) activity but express endogenous Na+/H+ exchange (NHE). We postulated that expression in oocytes of heterologous anion exchangers might allow regulatory volume increase (RVI) via functional coupling with endogenous NHE. Expression of neither erythroid nor kidney isoforms of AE1 conferred any form of RVI. In contrast, although AE2 expression did not confer primary RVI, it did confer on oocytes secondary RVI, with a requirement for hypotonic swelling before hypertonic shrinkage. This secondary RVI required extracellular Cl- and Na+, was blocked by 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid and amiloride, was bumetanide insensitive, and was blocked by prevention of intracellular alkalinization, all properties consistent with functional coupling of AE2-mediated Cl-/HCO3- exchange and endogenous NHE. RVI was unaffected by CO2-HCO3- or by partial oocyte Cl- depletion and was unrelated to the rate of oocyte shrinkage. Prior hypotonic swelling did not significantly alter subsequent hypertonic stimulation of AE2-mediated 36Cl influx or efflux. We conclude that heterologous AE2 expression suffices to confer volume regulation on Xenopus oocytes that lack intrinsic volume-regulatory mechanisms.

scholarly journals Interpolated twitches in fatiguing single mouse muscle fibres: implications for the assessment of central fatigue

2008 ◽  
Vol 586 (11) ◽  
pp. 2799-2805 ◽  
Author(s):  
Nicolas Place ◽  
Takashi Yamada ◽  
Joseph D. Bruton ◽  
Håkan Westerblad
Keyword(s):  
Central Fatigue ◽  
Muscle Fibres ◽  
Mouse Muscle

Ultrastructural localization of dystropin in human muscle by using gold immunolabelling

1990 ◽  
Vol 240 (1297) ◽  
pp. 197-210 ◽  
Keyword(s):  
Plasma Membrane ◽  
Ultrastructural Localization ◽  
Ultrastructural Level ◽  
Human Muscle ◽  
Muscle Fibres ◽  
Mouse Muscle ◽  
Transverse Tubular System ◽  
Cytoplasmic Face ◽  
Tubular System ◽  
Gold Probe

Immunolabelling with a 5 nm gold probe was used to localize dystrophin at the ultrastructural level in human muscle. The primary antibody was monoclonal, raised against a segment (amino acids 1181-1388) from the rod domain of dystrophin. The antibody (Dy4/6D3) is specific for dystrophin and shows no immunoreactivity with any protein from mdx mouse muscle or from patients with a gene deletion spanning part of the molecule recognized by the antibody (Nicholson et al . 1989 a ; England et al . 1990). Using this antibody, labelling was almost entirely confined to a narrow 75 nm rim at the periphery of the muscle fibres. Histograms of the distance from the gold probe to the cytoplasmic face of the plasma membrane and of the distance between gold probes (nearest neighbour in a plane parallel with the plasma membrane) displayed modes at approximately 15 nm and 120 nm, respectively. The distribution of the probe was the same in longitudinal and transverse sections of the muscle. These observations suggest that the rod portion of the dystrophin mole­cule is normally arranged close to the cytoplasmic face of the plasma membrane and that the molecules form an interconnecting network. Labelling was not associated with the transverse tubular system.

SRC family kinases in cell volume regulation

2005 ◽  
Vol 288 (3) ◽  
pp. C483-C493 ◽  
Author(s):  
David M. Cohen
Keyword(s):  
Tyrosine Kinases ◽  
Volume Regulation ◽  
Cell Volume Regulation ◽  
Src Family Kinases ◽  
Protein Tyrosine Kinases ◽  
Volume Increase ◽  
Regulatory Volume Increase ◽  
Hypotonic Stress ◽  
Cell Functions ◽  
Broad Role

SRC family kinases are a group of nine cytoplasmic protein tyrosine kinases essential for many cell functions. Some appear to be ubiquitously expressed, whereas others are highly tissue specific. The ability of members of the SRC family to influence ion transport has been recognized for several years. Mounting evidence suggests a broad role for SRC family kinases in the cell response to both hypertonic and hypotonic stress, and in the ensuing regulatory volume increase or decrease. In addition, members of this tyrosine kinase family participate in the mechanotransduction that accompanies cell membrane deformation. Finally, at least one SRC family member operates in concert with the p38 MAPK to regulate tonicity-dependent gene transcription.

scholarly journals rAAV-related therapy fully rescues myonuclear and myofilament function in X-linked myotubular myopathy

2020 ◽  
Vol 8 (1) ◽  
Author(s):  
Jacob A. Ross ◽  
Hichem Tasfaout ◽  
Yotam Levy ◽  
Jennifer Morgan ◽  
Belinda S. Cowling ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Contractile Function ◽  
Force Production ◽  
Muscle Disease ◽  
Synthetic Activity ◽  
Muscle Fibres ◽  
Mouse Muscle ◽  
Myotubular Myopathy ◽  
Irregular Spacing ◽  
And Function

Abstract X-linked myotubular myopathy (XLMTM) is a life-threatening skeletal muscle disease caused by mutations in the MTM1 gene. XLMTM fibres display a population of nuclei mispositioned in the centre. In the present study, we aimed to explore whether positioning and overall distribution of nuclei affects cellular organization and contractile function, thereby contributing to muscle weakness in this disease. We also assessed whether gene therapy alters nuclear arrangement and function. We used tissue from human patients and animal models, including XLMTM dogs that had received increasing doses of recombinant AAV8 vector restoring MTM1 expression (rAAV8-cMTM1). We then used single isolated muscle fibres to analyze nuclear organization and contractile function. In addition to the expected mislocalization of nuclei in the centre of muscle fibres, a novel form of nuclear mispositioning was observed: irregular spacing between those located at the fibre periphery, and an overall increased number of nuclei, leading to dramatically smaller and inconsistent myonuclear domains. Nuclear mislocalization was associated with decreases in global nuclear synthetic activity, contractile protein content and intrinsic myofilament force production. A contractile deficit originating at the myofilaments, rather than mechanical interference by centrally positioned nuclei, was supported by experiments in regenerated mouse muscle. Systemic administration of rAAV8-cMTM1 at doses higher than 2.5 × 1013 vg kg−1 allowed a full rescue of all these cellular defects in XLMTM dogs. Altogether, these findings identify previously unrecognized pathological mechanisms in human and animal XLMTM, associated with myonuclear defects and contractile filament function. These defects can be reversed by gene therapy restoring MTM1 expression in dogs with XLMTM.

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