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排序方式: 共有193条查询结果,搜索用时 906 毫秒
1.
Open-channel block by internally applied amines inhibits activation gate closure in batrachotoxin-activated sodium channels. 总被引:1,自引:1,他引:0 下载免费PDF全文
We have studied the action of several pore-blocking amines on voltage-dependent activation gating of batrachotoxin(BTX)-activated sodium channels, from bovine heart and rat skeletal muscle, incorporated into planar lipid bilayers. Although structurally simpler, the compounds studied show general structural features and channel-inhibiting actions that resemble those of lidocaine. When applied to the cytoplasmic end of the channel, these compounds cause a rapid, voltage-dependent, open-channel block seen as a reduction in apparent single-channel amplitude (companion paper). Internal application of phenylpropanolamine, phenylethylamine, phenylmethylamine, and diethylamine, as well as causing open-channel block, reduces the probability of channel closure, producing a shift of the steady-state activation curve toward more hyperpolarizing potentials. These gating effects were observed for both cardiac and skeletal muscle channels and were not evoked by addition of equimolar N-Methyl-D-Glucamine, suggesting a specific interaction of the blockers with the channel rather than a surface charge effect. Kinetic analysis of phenylpropanolamine action on skeletal muscle channels indicated that phenylpropanolamine reduced the closed probability via two separate mechanisms. First, mean closed durations were slightly abbreviated in its presence. Second, and more important, the frequency of the gating closures was reduced. This action was correlated with the degree, and the voltage dependence, of open-channel block, suggesting that the activation gate cannot close while the pore is occluded by the blocker. Such a mechanism might underlie the previously reported immobilization of gating charge associated with local anesthetic block of unmodified sodium channels. 相似文献
2.
Tribelli Paula M. Pezzoni Magdalena Brito María Gabriela Montesinos Nahuel V. Costa Cristina S. López Nancy I. 《Extremophiles : life under extreme conditions》2020,24(2):265-275
Extremophiles - Pseudomonas extremaustralis is an Antarctic bacterium with high stress resistance, able to grow under cold conditions. It is capable to produce polyhydroxyalkanoates (PHAs) mainly... 相似文献
3.
High voltage-activated (HVA) Cav channels form complexes with KCa1.1 channels, allowing reliable activation of KCa1.1 current through a nanodomain interaction. We recently found that low voltage-activated Cav3 calcium channels also create KCa1.1-Cav3 complexes. While coimmunoprecipitation studies again supported a nanodomain interaction, the sensitivity to calcium chelating agents was instead consistent with a microdomain interaction. A computational model of the KCa1.1-Cav3 complex suggested that multiple Cav3 channels were necessary to activate KCa1.1 channels, potentially causing the KCa1.1-Cav3 complex to be more susceptible to calcium chelators. Here, we expanded the model and compared it to a KCa1.1-Cav2.2 model to examine the role of Cav channel conductance and kinetics on KCa1.1 activation. As found for direct recordings, the voltage-dependent and kinetic properties of Cav3 channels were reflected in the activation of KCa1.1 current, including transient activation from lower voltages than other KCa1.1-Cav complexes. Substantial activation of KCa1.1 channels required the concerted activity of several Cav3.2 channels. Combined with the effect of EGTA, these results suggest that the Ca2+ domains of several KCa1.1-Cav3 complexes need to cooperate to generate sufficient [Ca2+]i, despite the physical association between KCa1.1 and Cav3 channels. By comparison, Cav2.2 channels were twice as effective at activating KCa1.1 channels and a single KCa1.1-Cav2.2 complex would be self-sufficient. However, even though Cav3 channels generate small, transient currents, the regulation of KCa1.1 activity by Cav3 channels is possible if multiple complexes cooperate through microdomain interactions. 相似文献
4.
Martha Sample Clare E. Aslan Nahuel Policelli Robert L. Sanford Erik Nielsen Martín A. Nuez 《Austral ecology》2019,44(8):1384-1397
Nonnative conifers are widespread in the southern hemisphere, where their use as plantation species has led to adverse ecosystem impacts sometimes intensified by invasion. Mechanical removal is a common strategy used to reduce or eliminate the negative impacts of nonnative conifers, and encourage native regeneration. However, a variety of factors may preclude active ecological restoration following removal. As a result, passive restoration – unassisted natural vegetation regeneration – is common following conifer removal. We asked, ‘what is the response of understorey cover to removal of nonnative conifer stands followed by passive restoration?' We sampled understorey cover in three site types: two‐ to ten‐year‐old clearcuts, native forest and current plantations. We then grouped understorey species by origin (native/nonnative) and growth form, and compared proportion and per cent cover of these groups as well as of bare ground and litter between the three site types. For clearcuts, we also analysed the effect of time since clearcut on the studied variables. We found that clearcuts had a significantly higher average proportion of nonnative understorey vegetation cover than native forest sites, where nonnative vegetation was nearly absent. The understorey of clearcut sites also averaged more overall vegetation cover and more nonnative vegetation cover (in particular nonnative shrubs and herbaceous species) than either plantation or native forest sites. Notably, 99% of nonnative shrub cover in clearcuts was the invasive nonnative species Scotch broom (Cytisus scoparius). After ten years of passive recovery since clearcutting, the proportion of understorey vegetation cover that is native has not increased and remains far below the proportion observed in native forest sites. Reduced natural regeneration capacity of the native ecosystem, presence of invasive species in the surrounding landscape and land‐use legacies from plantation forestry may inhibit native vegetation recovery and benefit opportunistic invasives, limiting the effectiveness of passive restoration in this context. Abstract in Spanish is available with online material. 相似文献
5.
6.
Feng ZP Hamid J Doering C Bosey GM Snutch TP Zamponi GW 《The Journal of biological chemistry》2001,276(19):15728-15735
We recently reported that amino acid residues contained within a putative EF hand motif in the domain III S5-H5 region of the alpha(1B) subunit affected the relative barium:calcium permeability of N-type calcium channels (Feng, Z. P., Hamid, J., Doering, C., Jarvis, S. E., Bosey, G. M., Bourinet, E., Snutch, T. P., and Zamponi, G. W. (2001) J. Biol. Chem. 276, 5726-5730). Since this region partially overlaps with residues previously implicated in block of the channel by omega-conotoxin GVIA, we assessed the effects of mutations in the putative EF hand domain on channel block by omega-conotoxin GVIA and the structurally related omega-conotoxin MVIIA. Both of the toxins irreversibly block the activity of wild type alpha(1B) N-type channels. We find that in addition to previously identified amino acid residues, residues in positions 1326 and 1332 are important determinants of omega-conotoxin GVIA blockade. Substitution of residue Glu(1332) to arginine slows the time course of development of block. Point mutations in position Gly(1326) to either arginine, glutamic acid, or proline dramatically decrease the time constant for development of the block. Additionally, in the G1326P mutant channel activity was almost completely recovered following washout. A qualitatively similar result was obtained with omega-conotoxin MVIIA, suggesting that common molecular determinants underlie block by these two toxins. Taken together the data suggest that residue Gly(1326) may form a barrier, which controls the access of peptide toxins to their blocking site within the outer vestibule of the channel pore and also stabilizes the toxin-channel interaction. 相似文献
7.
How would you make a drug that inhibits pain without side effects? The most obvious strategy for analgesia targets molecules that are expressed only on neurons used for pain. In this issue of Neuron, Bell et al. report a new splice variant of a calcium channel that controls neurotransmitter release and show that it is expressed primarily on nociceptors, the sensory neurons that trigger pain. 相似文献
8.
Perales M Parisi G Fornasari MS Colaneri A Villarreal F González-Schain N Echave J Gómez-Casati D Braun HP Araya A Zabaleta E 《Plant molecular biology》2004,56(6):947-957
We report the identification by two hybrid screens of two novel similar proteins, called Arabidopsis thaliana gamma carbonic anhydrase like1 and 2 (AtCAL1 and AtCAL2), that interact specifically with putative Arabidopsis thaliana gamma Carbonic Anhydrase (AtCA) proteins in plant mitochondria. The interaction region that was located in the N-terminal 150 amino acids of mature AtCA and AtCA like proteins represents a new interaction domain. In vitro experiments indicate that these proteins are imported into mitochondria and are associated with mitochondrial complex I as AtCAs. All plant species analyzed contain both AtCA and AtCAL sequences indicating that these genes were conserved throughout plant evolution. Structural modeling of AtCAL sequences show a deviation of functionally important active site residues with respect to CAs but could form active interfaces in the interaction with AtCAs. We postulate a CA complex tightly associated to plant mitochondrial complex. 相似文献
9.
Szule JA Jarvis SE Hibbert JE Spafford JD Braun JE Zamponi GW Wessel GM Coorssen JR 《The Journal of biological chemistry》2003,278(27):24251-24254
Complexes of specific presynaptic proteins have been hypothesized to drive or catalyze the membrane fusion steps of exocytosis. Here we use a stage-specific preparation to test the roles of SNAREs, synaptotagmin, and SNARE-binding proteins in the mechanism of Ca2+-triggered membrane fusion. Excess exogenous proteins, sufficient to block SNARE interactions, did not inhibit either the Ca2+ sensitivity, extent, or kinetics of fusion. In contrast, despite a limited effect on SNARE and synaptotagmin densities, treatments with high doses of chymotrypsin markedly inhibited fusion. Conversely, low doses of chymotrypsin had no effect on the Ca2+ sensitivity or extent of fusion but did alter the kinetic profile, indicating a more direct involvement of other proteins in the triggered fusion pathway. SNAREs, synaptotagmin, and their immediate binding partners are critical to exocytosis at a stage other than membrane fusion, although they may still influence the triggered steps. 相似文献
10.
Altier C Dubel SJ Barrère C Jarvis SE Stotz SC Spaetgens RL Scott JD Cornet V De Waard M Zamponi GW Nargeot J Bourinet E 《The Journal of biological chemistry》2002,277(37):33598-33603
Accurate calcium signaling requires spatial and temporal coordination of voltage-gated calcium channels (VGCCs) and a variety of signal transduction proteins. Accordingly, regulation of L-type VGCCs involves the assembly of complexes that include the channel subunits, protein kinase A (PKA), protein kinase A anchoring proteins (AKAPs), and beta2-adrenergic receptors, although the molecular details underlying these interactions remain enigmatic. We show here, by combining extracellular epitope splicing into the channel pore-forming subunit and immunoassays with whole cell and single channel electrophysiological recordings, that AKAP79 directly regulates cell surface expression of L-type calcium channels independently of PKA. This regulation involves a short polyproline sequence contained specifically within the II-III cytoplasmic loop of the channel. Thus we propose a novel mechanism whereby AKAP79 and L-type VGCCs function as components of a biosynthetic mechanism that favors membrane incorporation of organized molecular complexes in a manner that is independent of PKA phosphorylation events. 相似文献