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191.
目的:通过建立右室流出道室速(RVOT-VT)的动物模型,以L型钙通道α1c蛋白作为观察指标,观察RVOT-VT时对L型钙通道α1c蛋白表达的影响,旨在探讨L型钙通道在RVOT-VT中的作用。方法:健康新西兰大耳白兔30只,随机分三组,分别为对照组(10只)、室速组(10只)、室速加维拉帕米干预组(10只)。采用免疫组织化学的方法对三组实验动物的右室流出道心肌组织进行L型钙通道cdc蛋白表达的检测。结果:1、高频刺激主动脉与肺动脉交界处均诱发了起源于右室流出道部位的室速,且室速持续时间均大于4小时。2、室速组L型钙通道α1c蛋白表达量明显下降;干预组L型钙通道α1cc蛋白的表达下降,但与对照组比较无显著差异。结论:1、室速组的心肌L型钙通道α1c蛋白表达发生了重构。2、维拉帕米可以改善心肌L型钙通道α1c蛋白的重构。3、L型钙通道在RVOT-VT发生、持续中起重要作用。 相似文献
192.
急性低氧对豚鼠心室肌细胞L型钙通道的影响 总被引:11,自引:1,他引:11
应用常规膜片箝全细胞记录技术,研究心肌细胞的内向钙离子流时,钙通道的″RunDown″现象使记录时间较短,难以进行适当的实验分析。在分离的豚鼠心室肌细胞上应用制霉菌素全细胞记录技术,可减少″RunDown″现象,内向L-型钙电流可保持稳定达100min以上,显示内源性钙离子缓冲机制保持稳定。应用制霉菌素全细胞记录技术,急性低氧10min(Po24±0.7kPa),L-型钙电流被抑制(钙电流峰值降低),电压-电流曲线上移。复氧10min后,内向钙电流不能恢复,峰值低于对照水平。结果提示:急性低氧引起的心肌动作电位时程(APD)缩短时,不仅外向钾电流增加,而且也伴有内向钙电流的抑制过程,这些现象可能与心肌细胞的L-型钙通道的磷酸化在低氧时的部分抑制有关。 相似文献
193.
The primary receptor neurons of the auditory, vestibular, and visual systems encode a broad range of sensory information by
modulating the tonic release of the neurotransmitter glutamate in response to graded changes in membrane potential. The output
synapses of these neurons are marked by structures called synaptic ribbons, which tether a pool of releasable synaptic vesicles
at the active zone where glutamate release occurs in response to calcium influx through L-type channels. Ribbons are composed
primarily of the protein, RIBEYE, which is unique to ribbon synapses, but cytomatrix proteins that regulate the vesicle cycle
in conventional terminals, such as Piccolo and Bassoon, also are found at ribbons. Conventional and ribbon terminals differ,
however, in the size, molecular composition, and mobilization of their synaptic vesicle pools. Calcium-binding proteins and
plasma membrane calcium pumps, together with endomembrane pumps and channels, play important roles in calcium handling at
ribbon synapses. Taken together, emerging evidence suggests that several molecular and cellular specializations work in concert
to support the sustained exocytosis of glutamate that is a hallmark of ribbon synapses. Consistent with its functional importance,
abnormalities in a variety of functional aspects of the ribbon presynaptic terminal underlie several forms of auditory neuropathy
and retinopathy. 相似文献
194.
《朊病毒》2013,7(1):89-93
L-type bovine spongiform encephalopathy (BSE) is an atypical form of BSE. To characterize the Japanese L-type BSE prion, we conducted a comparative study of the Japanese and foreign L-type BSE isolates. The L-type BSE isolates of Japan, Germany, France and Canada were intracerebrally inoculated into bovinized prion protein-overexpressing transgenic mice (TgBoPrP). All the examined L-type BSE isolates were transmitted to TgBoPrP mice, and no clear differences were observed in their biological and biochemical properties. Here, we present evidence that the Japanese and Canadian L-type BSE prions are identical to those from the European cases. 相似文献
195.
John Szpyt Nancy Lorenzon Claudio F. Perez Ethan Norris Paul D. Allen Kurt G. Beam Montserrat Samsó 《The Journal of biological chemistry》2012,287(52):43853-43861
The L-type Ca2+ channel (dihydropyridine receptor (DHPR) in skeletal muscle acts as the voltage sensor for excitation-contraction coupling. To better resolve the spatial organization of the DHPR subunits (α1s or CaV1.1, α2, β1a, δ1, and γ), we created transgenic mice expressing a recombinant β1a subunit with YFP and a biotin acceptor domain attached to its N- and C- termini, respectively. DHPR complexes were purified from skeletal muscle, negatively stained, imaged by electron microscopy, and subjected to single-particle image analysis. The resulting 19.1-Å resolution, three-dimensional reconstruction shows a main body of 17 × 11 × 8 nm with five corners along its perimeter. Two protrusions emerge from either face of the main body: the larger one attributed to the α2-δ1 subunit that forms a flexible hook-shaped feature and a smaller protrusion on the opposite side that corresponds to the II-III loop of CaV1.1 as revealed by antibody labeling. Novel features discernible in the electron density accommodate the atomic coordinates of a voltage-gated sodium channel and of the β subunit in a single docking possibility that defines the α1-β interaction. The β subunit appears more closely associated to the membrane than expected, which may better account for both its role in localizing the α1s subunit to the membrane and its suggested role in excitation-contraction coupling. 相似文献
196.
Inactivation of L-type Ca channels (LTCC) is regulated by both Ca and voltage-dependent processes (CDI and VDI). To differentiate VDI and CDI, several experimental and theoretical studies have considered the inactivation of Ba current through LTCC (IBa) as a measure of VDI. However, there is evidence that Ba can weakly mimic Ca, such that IBa inactivation is still a mixture of CDI and VDI. To avoid this complication, some have used the monovalent cation current through LTCC (INS), which can be measured when divalent cation concentrations are very low. Notably, INS inactivation rate does not depend on current amplitude, and hence may reflect purely VDI. However, based on analysis of existent and new data, and modeling, we find that INS can inactivate more rapidly and completely than IBa, especially at physiological temperature. Thus VDI that occurs during IBa (or ICa) must differ intrinsically from VDI during INS. To account for this, we have extended a previously published LTCC mathematical model of VDI and CDI into an excitation-contraction coupling model, and assessed whether and how experimental IBa inactivation results (traditionally used in VDI experiments and models) could be recapitulated by modifying CDI to account for Ba-dependent inactivation. Thus, the view of a slow and incomplete INS inactivation should be revised, and INS inactivation is a poor measure of VDI during ICa or IBa. This complicates VDI analysis experimentally, but raises intriguing new questions about how the molecular mechanisms of VDI differ for divalent and monovalent currents through LTCCs. 相似文献
197.
《Channels (Austin, Tex.)》2013,7(5):298-306
Proper function of Cav1.4 L-type calcium channels is crucial for neurotransmitter release in the retina. Our understanding about how different levels of Cav1.4 channel activity affect retinal function is still limited. In the gain-of-function mouse model Cav1.4-IT we expected a reduction in the photoreceptor dynamic range but still transmission toward retinal ganglion cells. A fraction of Cav1.4-IT ganglion cells responded to light stimulation in multielectrode array recordings from whole-mounted retinas, but showed a significantly delayed response onset. Another significant number of cells showed higher activity in darkness. In addition to structural remodeling observed at the first retinal synapse of Cav1.4-IT mice the functional data suggested a loss of contrast enhancement, a fundamental feature of our visual system. In fact, Cav1.4-IT mouse retinas showed a decline in spatial response and changes in their contrast sensitivity profile. Photoreceptor degeneration was obvious from the nodular structure of cone axons and enlarged pedicles which partly moved toward the outer nuclear layer. Loss of photoreceptors was also expressed as reduced expression of proteins involved in chemical and electrical transmission, as such metabotropic glutamate receptor mGluR6 and the gap junction protein Connexin 36. Such gross changes in retinal structure and function could also explain the diminished visual performance of CSNB2 patients. The expression pattern of the plasma-membrane calcium ATPase 1 which participates in the maintenance of the intracellular calcium homeostasis in photoreceptors was changed in Cav1.4-IT mice. This might be part of a protection mechanism against increased calcium influx, as this is suggested for Cav1.4-IT channels. 相似文献
198.
In previous works, we have shown that L-type voltage-operated calcium channels, N-methyl-d-aspartate receptors (NMDAr), neuronal nitric oxide synthase (nNOS) and cytochrome b5 reductase (Cb5R) co-localize within the same lipid rafts-associated nanodomains in mature cerebellar granule neurons (CGN). In this work, we show that the calcium transport systems of the plasma membrane extruding calcium from the cytosol, plasma membrane calcium pumps (PMCA) and sodium–calcium exchangers (NCX), are also associated with these nanodomains. All these proteins were found to co-immunoprecipitate with caveolin-1 after treatment with 25 mM methyl-β-cyclodextrin, a lipid rafts solubilizing agent. However, the treatment of CGN with methyl-β-cyclodextrin largely attenuated the rise of cytosolic calcium induced by l-glutamate through NMDAr. Fluorescence energy transfer imaging revealed that all of them are present in sub-microdomains of a size smaller than 200 nm, with a peripheral distribution of the calcium extrusion systems PMCA and NCX. Fluorescence microscopy images analysis revealed high calcium dynamic sub-microcompartments near the plasma membrane in fura-2-loaded CGN at short times after addition of l-glutamate. In addition, the close proximity between sources of nitric oxide (nNOS) and superoxide anion (Cb5R) suggests that these nanodomains are involved in the fast and efficient cross-talk between calcium and redox signaling in neurons. 相似文献
199.
Hugh J. L. Fryer Ronald J. Knox Stephen M. Strittmatter Robert Kalb 《Journal of neurochemistry》1999,72(2):500-513
Abstract : We have used cultures of purified embryonic rat spinal cord motor neurons to study the neurotoxic effects of prolonged ionotropic glutamate receptor activation. NMDA and non-NMDA glutamate receptor agonists kill a maximum of 40% of the motor neurons in a concentration- and time-dependent manner, which can be blocked by receptor subtype-specific antagonists. subunit-specific antibodies stain all of the motor neurons with approximately the same intensity and for the same repertoire of subunits, suggesting that the survival of the nonvulnerable population is unlikely to be due to the lack of glutamate receptor expression. Extracellular Ca2+ is required for excitotoxicity, and the route of entry initiated by activation of non-NMDA, but not NMDA, receptors is L-type Ca2+ channels. Ca2+ imaging of motor neurons after application of specific glutamate receptor agonists reveals a sustained rise in intracellular Ca2+ that is present to a similar degree in most motor neurons, and can be blocked by appropriate receptor/channel antagonists. Although the lethal effects of glutamate receptor agonists are seen in only a subset of cultured motor neurons, the basis of this selectivity is unlikely to be simply the glutamate receptor phenotype or the level/pattern of rise in agonist-evoked intracellular Ca2+ . 相似文献
200.
Disruption of phospholipase C-β (PLC) by the norpA mutations of Drosophila renders flies blind by affecting the light-evoked photoreceptor potential. We report here that the norpA-coded PLC modulates the 1,4-dihydropyridine (DHP)-sensitive Ca2+ channels in larval muscles. The DHP-sensitive current was reduced in the norpA mutants. Application of 1 μM phorbol 12-myristate 13-acetate (TPA) and 1 μM phorbol 12,13-didecanoate (PDD), activators of protein kinase C (PKC), rescued the current in the mutant fibers without significantly affecting the normal current. 4α-phorbol 12,13-didecanoate (4αPDD), an inactive analog of PDD, did not affect either the normal or the mutant current. One micromolar bisindolylmaleimide (BIM), an inhibitor of PKC, reduced the current in the normal fibers without affecting the mutant current. 300 μM sn-1,2-dioctanoyl-glycerol (DOG), an analog of diacylglycerol (DAG), increased the current in the mutant fibers. These experiments suggest that the DHP-sensitive Ca2+ channels in Drosophila may be modulated by the PLC-DAG-PKC pathway, and that the same PLC isozyme which is involved in phototransduction in the adult flies may also modulate muscle Ca2+ channels in the larval stage of development. © 1997 John Wiley & Sons, Inc. J Neurobiol 33: 265–275, 1997 相似文献