抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Muscle fatigue is an exercise-induced reduction in maximal voluntary muscle force. It may arise not only because of peripheral changes at the level of the muscle, but also because the central nervous system fails to drive the motoneurons adequately. Evidence for “central” fatigue and the neural mechanisms underlying it are reviewed, together with its terminology and the methods used to reveal it. Much data suggest that voluntary activation of human motoneurons and muscle fibers is suboptimal and thus maximal voluntary force is commonly less than true maximal force. Hence, maximal voluntary strength can often be below true maximal muscle force. The technique of twitch interpolation has helped to reveal the changes in drive to motoneurons during fatigue. Voluntary activation usually diminishes during maximal voluntary isometric tasks, that is central fatigue develops, and motor unit firing rates decline. Transcranial magnetic stimulation over the motor cortex during fatiguing exercise has revealed focal cha...

Spinal and Supraspinal Factors in Human Muscle Fatigue

Lang, Florian, Gillian L. Busch, Markus Ritter, Harald Volkl, Siegfried Waldegger, Erich Gulbins, and Dieter Haussinger. Functional Significance of Cell Volume Regulatory Mechanisms. Physiol. Rev. ...

Functional Significance of Cell Volume Regulatory Mechanisms

The ability to control cell volume is pivotal for cell function. Cell volume perturbation elicits a wide array of signaling events, leading to protective (e.g., cytoskeletal rearrangement) and adap...

Physiology of cell volume regulation in vertebrates.

Cl− channels reside both in the plasma membrane and in intracellular organelles Their functions range from ion homeostasis to cell volume regulation, transepithelial transport, and regulation of e

https://www.leibniz-fmp.de/fileadmin/user_upload/Physiology_and_Pathology_of_Ion_Transport/documents/PhysRev2002.pdf

Molecular Structure and Physiological Function of Chloride Channels

Marked increase in cell permeability ascribed to open connexin (Cx)43 hemichannels is induced by metabolic inhibition (MI) of cortical astrocytes in culture, but the molecular mechanisms are not established. Dephosphorylation and/or oxidation of Cx43 hemichannels was proposed as a potential mechanism to increase their open probability. We now demonstrate that MI increases the number of hemichannels on the cell surface assayed by biotinylation and Western blot, and that this change is followed by increased dephosphorylation and S-nitrosylation. The increase in rate of dye uptake caused by MI is comparable to the increase in surface expression; thus, open probability and permeation per hemichannel may be unchanged. Reducing agents did not affect dephosphorylation of Cx43 hemichannels but reduced dye uptake and S-nitrosylation. Uptake was also reduced by elevated intracellular but not extracellular levels of reduced glutathione. Moreover, nitric oxide donors induced dye uptake and nitrosylation of surface Cx43 but did not affect its abundance or phosphorylation. Thus, permeability per channel is increased, presumably because of increase in open probability. We propose that increased dye uptake induced by MI is mediated by an increased number of Cx43 hemichannels in the surface and is associated with multiple molecular changes, among which nitrosylation of intracellular Cx43 cysteine residues may be a critical factor.

https://www.pnas.org/content/pnas/103/12/4475.full.pdf

S-nitrosylation and permeation through connexin 43 hemichannels in astrocytes: Induction by oxidant stress and reversal by reducing agents

Regulation of Purified and Reconstituted Connexin 43 Hemichannels by Protein Kinase C-mediated Phosphorylation of Serine 368

Microelectrode techniques were employed to measure the electrical resistance of the cell membranes and the shunt pathway, and the equivalent electromotive forces (EMF's) at both cell borders in Necturus gallbladder epithelium. The cell is, on the average, 57 mV negative to the mucosal solution and 59 mV negative to the serosal solution. The transepithelial potential (Vms) ranges from 0.5 to 5 mV, serosal solution positive. Assuming that the shunt EMF (Vs) is zero with standard Ringer's bathing oth sides of the tissue, both cell membrane EMF's are oriented with the negative pole toward the cell interior and are 39.9 +/- 3.6 mV (apical, Va), and 69.4 +/- 1.8 mV (basal-lateral, Vb)...

Electrical properties of the cellular transepithelial pathway in Necturus gallbladder. I. Circuit analysis and steady-state effects of mucosal solution ionic substitutions.

Phosphorylation of the gap junction protein connexin 43 (Cx43) by protein kinase C (PKC) decreases dye coupling in many cell types. We report an investigation of the regulation by PKC of Cx43 gap j...

Mechanism of regulation of the gap junction protein connexin 43 by protein kinase C-mediated phosphorylation

The effects of theophylline, 8-Br-cAMP, and cAMP on necturus gallbladder epithelium were investigated using microelectrode techniques. Each of these substances depolarized the cell membranes by approximately 15 mV and decreased the apparent ratio of apical to basolateral membrane resistances to a value not significantly different from zero. Examination of the ionic selectivity of the apical membrane by ion substitutions in the mucosal bathing medium revealed a large increase in Cl permeability with no apparent changes in K and Na permeabilities. Intracellular Cl activity ((a)CL(i)) was measured using Cl- sensitive liquid ion-exchanger microelectrodes. Under control conditions, (a)Cl(i) was approximately 20 mM, 2.5 times higher than the value expected for equilibrium distribution ((a)Cl(i/eq). After addition of 8-Br-cAMP, (a)Cl(i) decreased within less than 60 s to approximately 13 mM, a value not significantly different from ((a)Cl(i/eq)). Virtually identical results were obtained with theophylline. Under control conditions, luminal Cl removal caused (a)Cl(i) to fall at an initial rate of 1.8 mM/min, whereas in tissues exposed to 8-Br- cAMP or theophylline a rate of 11.6 mM/min was observed. The apical membrane Cl transference number was estimated from the change of (a)Cl(i) upon exposure to 8-Br-cAMP as well as from the changes in apical membrane potential during variation of the luminal Cl concentration. The results, 0.91 and 0.88, respectively, are indicative of a high Cl permeability of the apical membrane during cAMP. This effect may explain, at least in part, the complete inhibition of fluid absorption produced by theophylline in this tissue. Moreover, enhancement of apical membrane Cl permeability may account for a variety of cAMP effects in epithelial tissues.

/pdf/cyclic-amp-induced-chloride-permeability-in-the-apical-2dygmvmnif.pdf

Luis Reuss

Papers

S-nitrosylation and permeation through connexin 43 hemichannels in astrocytes: Induction by oxidant stress and reversal by reducing agents

Regulation of Purified and Reconstituted Connexin 43 Hemichannels by Protein Kinase C-mediated Phosphorylation of Serine 368

Electrical properties of the cellular transepithelial pathway in Necturus gallbladder. I. Circuit analysis and steady-state effects of mucosal solution ionic substitutions.

Mechanism of regulation of the gap junction protein connexin 43 by protein kinase C-mediated phosphorylation

Cyclic AMP-induced chloride permeability in the apical membrane of Necturus gallbladder epithelium.