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981.
Sancar F Touroutine D Gao S Oh HJ Gendrel M Bessereau JL Kim H Zhen M Richmond JE 《The Journal of biological chemistry》2011,286(38):33501-33510
The dystrophin-associated protein complex (DAPC) consists of several transmembrane and intracellular scaffolding elements that have been implicated in maintaining the structure and morphology of the vertebrate neuromuscular junction (NMJ). Genetic linkage analysis has identified loss-of-function mutations in DAPC genes that give rise to degenerative muscular dystrophies. Although much is known about the involvement of the DAPC in maintaining muscle integrity, less is known about the precise contribution of the DAPC in cell signaling events. To better characterize the functional role of the DAPC at the NMJ, we used electrophysiology, immunohistochemistry, and fluorescent labeling to directly assess cholinergic synaptic transmission, ion channel localization, and muscle excitability in loss-of-function (lf) mutants of Caenorhabditis elegans DAPC homologues. We found that all DAPC mutants consistently display mislocalization of the Ca(2+)-gated K(+) channel, SLO-1, in muscle cells, while ionotropic acetylcholine receptor (AChR) expression and localization at the NMJ remained unaltered. Synaptic cholinergic signaling was also not significantly impacted across DAPC(lf) mutants. Consistent with these findings and the postsynaptic mislocalization of SLO-1, we observed an increase in muscle excitability downstream of cholinergic signaling. Based on our results, we conclude that the DAPC is not involved in regulating AChR architecture at the NMJ, but rather functions to control muscle excitability, in an activity-dependent manner, through the proper localization of SLO-1 channels. 相似文献
982.
Philip J. White 《Planta》1994,193(2):186-193
Plasma-membrane vesicles were purified by aqueous-polymer two-phase partitioning of a microsomal membrane fraction from rye (Secale cereale L.) roots and incorporated into planar 1-palmitoyl-2-oleoyl phosphatidylethanolamine bilayers. A voltage-dependent cation-channel became incorporated into the bilayer with its cytoplasmic surface facing the trans compartment (which was grounded) and was characterized from single-channel recordings. The channel had a unitary conductance of 174 pS in symmetrical 100 mM KCl. The selectivity towards monovalent cations, determined from both conductance measurements in symmetrical 100 mM cation chloride and from permeability ratios in the presence of (cis: trans) 100 mM cation chloride: 100 mM KCl, was CsKRb>Na. The channel was also permeable to both Ba2+ and Ca2+. Although the unitary conductances in symmetrical 100 mM BaCl2 and CaCl2 were only 46 pS and 40 pS, respectively, the apparent permeabilities of the divalent cations relative to K+ were greater than expected (PKPBaPCa, 1.001.662.60). This anomaly might result from competition between divalent and monovalent cations for an intrapore binding site. The channel exhibited complex gating kinetics, which were modulated in response to changes in the zero-current (reversal) potential of the channel (Erev). In symmetrical 100 mM KCl the channel inactivated at positive voltages greater than 100 mV and the activated channel exhibited a high probability of being in an open-state (P0>0.90) at all voltages between ±100 mV. Channel P0 approximated unity at voltages in the range -60 to +20 mV. As more-negative voltages were applied, P0 decreased gradually. In contrast, as more positive voltages were applied, P0 decreased initially to a local minimum (approaching P0=0.90), then increased as the voltage was further increased before declining at extreme positive voltages. Under physiologically relevant ionic conditions, with 100 mM KCl plus contaminant Ca2+ on the trans (cytoplasmic) side and 1 mM KCl plus 2 mM CaCl2 on the cis (extracellular) side of the channel, Erev was 25.2 mV and the relative permeability PCa/PK was 7.45. Thus, the channel would be activated by plasma-membrane depolarization in vivo and facilitate Ca2+ influx and net K+ efflux. A role in intracellular signalling is proposed for this channel. It could open in response to stimuli which depolarize the plasma membrane, allowing Ca2+ into the cytoplasm and, thereby, initiating a cellular response. The outward K+ current would act to stabilize the trans-plasma membrane voltage, preventing excessive depolarization during Ca2+ influx.Abbreviations and Symbols EK
Nernst (equilibrium) potential for potassium ions
- Erev
zero-current (reversal) potential of the channel
- c
apparent mean lifetime of the activated-channel closed-state
- o
apparent mean lifetime of the activated-channel open-state
- PE
dephosphatidylethanolamine
- PO
probability of finding the activated channel in an open-state
This work was supported by the Agriculture and Food Research Council and by a grant from the Science and Engineering Research Council Membrane Initiative (GR/F 33971) to Prof. E.A.C. MacRobbie (University of Cambridge). 相似文献
983.
The mouse diaphragm muscle fiber was studied using the loose patch clamp technique. The voltage gated sodium currents were evoked by step pulses from a holding potential of about −70 mV. Following the activation of the sodium current, a very large and fast outward current was evoked. The sensitivity of this current to 4-aminopyridine and tetraethylammonium indicates the potassium ion as the possible carrier for the channel. Furthermore, the sensitivity to tetrodotoxin and extracellular sodium demonstrated the sodium dependence of this current. 相似文献
984.
Patricia Preston Lena Wartosch Dorothee G��nzel Michael Fromm Patthara Kongsuphol Jiraporn Ousingsawat Karl Kunzelmann Jacques Barhanin Richard Warth Thomas J. Jentsch 《The Journal of biological chemistry》2010,285(10):7165-7175
The KCNE3 β-subunit constitutively opens outwardly rectifying KCNQ1 (Kv7.1) K+ channels by abolishing their voltage-dependent gating. The resulting KCNQ1/KCNE3 heteromers display enhanced sensitivity to K+ channel inhibitors like chromanol 293B. KCNE3 was also suggested to modify biophysical properties of several other K+ channels, and a mutation in KCNE3 was proposed to underlie forms of human periodic paralysis. To investigate physiological roles of KCNE3, we now disrupted its gene in mice. kcne3−/− mice were viable and fertile and displayed neither periodic paralysis nor other obvious skeletal muscle abnormalities. KCNQ1/KCNE3 heteromers are present in basolateral membranes of intestinal and tracheal epithelial cells where they might facilitate transepithelial Cl− secretion through basolateral recycling of K+ ions and by increasing the electrochemical driving force for apical Cl− exit. Indeed, cAMP-stimulated electrogenic Cl− secretion across tracheal and intestinal epithelia was drastically reduced in kcne3−/− mice. Because the abundance and subcellular localization of KCNQ1 was unchanged in kcne3−/− mice, the modification of biophysical properties of KCNQ1 by KCNE3 is essential for its role in intestinal and tracheal transport. Further, these results suggest KCNE3 as a potential modifier gene in cystic fibrosis. 相似文献
985.
Anetor JI Asiribo OA Adedapo KS Akingbola TS Olorunnisola OS Adeniyi FA 《Biological trace element research》2007,120(1-3):19-27
Oxidative stress is an important component of diabetes and its complications. Manganese (Mn), the key component of the Mitochondrial
antioxidant (MnSOD), plays a key role in the superoxide uncoupling protein 2 (UCP-2) pathway in inhibiting of glucose-stimulated
insulin secretion (GSIS). The interactions of Mn with ascorbate and other components of this pathway have not been defined
in type-2 diabetes. Fifty established type 2 diabetics (30 males, 20 females) and 30 non-diabetics (controls; 18 males, 12
females) matched for age and sex were investigated. Dietary intake, particularly of micronutrients as assessed by 24-h dietary
recall was similar between diabetics and controls. Weight and height of all subjects were determined and body mass index (BMI)
computed after clinical assessment. Fasting plasma glucose, manganese, ascorbic acid, creatinine and K+ levels were determined; K+ was to assess the K+ channels, whereas creatinine was to assess probability of oxidative stress nephropathy. Body mass index was greater in DM
than in controls (p < 0.001). Fasting plasma glucose and Mn levels (p < 0.00 and p < 0.01, respectively) were higher in diabetes than in the controls. Manganese level was greater than twice the levels in
controls. Ascorbic acid was not significantly different (p > 0.05), but was 50% lower than the level in non-diabetics. Potassium like Mn and glucose was significantly higher in diabetes
mellitus (DM) than in controls (p < 0.001). Creatinine was not significantly different between diabetics and controls (p > 0.05). Correlations among all parameters were not significantly different. These findings suggest absence of significant
oxidative stress in the mitochondria, probably excluding a role for UCP-2-superoxide pathway in the inhibition of glucose-stimulated
insulin secretion (GSIS), calling for caution in the precocious conclusion that interruption of UCP-2 activity may provide
a viable strategy to improve β-cell dysfunction in type 2 diabetes mellitus. 相似文献
986.
987.
羊草草原土壤中N、P、K含量的季节变化规律是生长季初期较高,6-8月生长旺季较低,生长季末再度升高。营养元素在植物体内的分配是地下部分大于地上部分。地下部分N的贮量为地上部分的3.6倍,K为2.9倍,P为2.8倍。地上部分3种元素含量的季节变化曲线呈单峰型,从生长初期开始上升,最大值出现在8月,生长末期逐渐下降。地下部分的季节变化规律,大体上在整个生长季内呈上升趋势,随着根系的生长,营养元素的积累量不断增加。对植物-土壤之间营养元素动态分析结果表明,随着时间的推移,N、P、K在备状态中的比例趋于恒定。在稳定状态下,3种元素在土壤中的比例逐渐减少,与初始量相比N、P、K的含量分别减少21.23%、5.14%和2.99%。在其它状态中,3种元素的含量均有提高,特别在枯枝落叶和死根中增加的幅度较大。 相似文献
988.
Glycine betaine stimulates the growth rate of various bacteria in high osmolarity medium. In our studies, glycine betaine stimulated the growth rate of Escherichia coli K 12 in minimal medium with normal osmolarity at alkaline pH (pH 8.2). Betaine also caused a reduction in the intracellular pools of K+ and low molecular weight thiols in E. coli growing both in medium with high osmolarity and at alkaline pH. These effects of betaine were absent at pH 7.0. In cells growing in high osmolarity medium, 10 mM sodium acetate or 10 M N-ethylmaleimide reduced expression of the osmosensitive gene proU to the same extent as treatment with betaine; however, under these conditions, sodium acetate and N-ethylmaleimide did not stimulate the growth of E. coli. It is proposed that low molecular weight thiols and intracellular pH may participate in the response of E. coli to betaine. 相似文献
989.
Alexandra Mant Sarah Williams Laura Roncoroni Eleanor Lowry Daniel Johnson Ita O'Kelly 《The Journal of biological chemistry》2013,288(5):3251-3264
Two-pore domain potassium (K2P) channels play fundamental roles in cellular processes by enabling a constitutive leak of potassium from cells in which they are expressed, thus influencing cellular membrane potential and activity. Hence, regulation of these channels is of critical importance to cellular function. A key regulatory mechanism of K2P channels is the control of their cell surface expression. Membrane protein delivery to and retrieval from the cell surface is controlled by their passage through the secretory and endocytic pathways, and post-translational modifications regulate their progression through these pathways. All but one of the K2P channels possess consensus N-linked glycosylation sites, and here we demonstrate that the conserved putative N-glycosylation site in K2P3.1 and K2P9.1 is a glycan acceptor site. Patch clamp analysis revealed that disruption of channel glycosylation reduced K2P3.1 current, and flow cytometry was instrumental in attributing this to a decreased number of channels on the cell surface. Similar findings were observed when cells were cultured in reduced glucose concentrations. Disruption of N-linked glycosylation has less of an effect on K2P9.1, with a small reduction in number of channels on the surface observed, but no functional implications detected. Because nonglycosylated channels appear to pass through the secretory pathway in a manner comparable with glycosylated channels, the evidence presented here suggests that the decreased number of nonglycosylated K2P3.1 channels on the cell surface may be due to their decreased stability. 相似文献
990.
The effects of a penetrating (NEM) and a non-penetrating (PCMBS) sulfhydryl-specific reagent on proton extrusion, 86Rb and [U-14C]sucrose uptake by Vicia faba leaves have been studied. Proton extrusion was strongly or completely inhibited by 0.1 mM NEM. 86Rb and [U-14C]sucrose uptake were markedly reduced by NEM concentrations equal to or higher than 0.5 mM. Under our experimental conditions, PCMBS (1 mM) exerted a strong inhibition on [14C]sucrose uptake but did not inhibit proton extrusion and 86Rb uptake. The sensitivity of phloem loading to PCMBS is thought to be a consequence of sugar-carrier blockage and not of inhibition of the proton pump.Abbreviations CCCP
carbonylcyanide-m-chlorophenylhydrazone
- DES
diethylstilbestrol
- DCCD
dicyclohexylcarbodiimide
- FC
Fusicoccin
- NEM
N-ethylmaleimide
- PCMBS
p-chloromercuribenzenesulfonic acid 相似文献