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41.
Three types of electrical excitation have been investigated in the marine diatom Coscinodiscus wailesii. I: Depolarization-triggered, transient Cl− conductance, G
Cl
(t), followed by a transient, voltage-gated K+ conductance, G
K
, with an active state a and two inactive states i
1 and i
2 in series (a-i
1-i
2). II: Similar G
Cl
(t) as in Type-I but triggered by hyperpolarization; a subsequent increase of G
K
in this type is indicated but not analyzed in detail. III: Hyperpolarization-induced transient of a voltage-gated activity
of an electrogenic pump (i
2-a-i
2), followed by G
Cl
(t) as in Type-II excitations. Type-III with pump gating is novel as such. G
Cl
(t) in all types seems to reflect the mechanism of InsP−
3 and Ca2+-mediated G
Cl
(t) in the action potential in Chara (Biskup et al., 1999). The nonlinear current-voltage-time relationships of Type-I and Type-III excitations have been recorded
under voltage-clamp using single saw-tooth command voltages (voltage range: −200 to +50 mV, typical slope: ±1 Vs−1). Fits of the corresponding models to the experimental data provided numerical values of the model parameters. The statistical
significance of these solutions is investigated. We suggest that the original function of electrical excitability of biological
membranes is related to osmoregulation which has persisted through evolution in plants, whereas the familiar and osmotically
neutral action potentials in animals have evolved later towards the novel function of rapid transmission of information over
long distances.
Received: 2 December 1999/Revised: 3 March 2000 相似文献
42.
The Mouse GalR2 Galanin Receptor: Genomic Organization, cDNA Cloning, and Functional Characterization 总被引:2,自引:1,他引:1
Ling Pang Tanaz Hashemi Hu-Jung J. Lee Maureen Maguire Michael P. Graziano Marvin Bayne Brian Hawes Gwendolyn Wong Suke Wang 《Journal of neurochemistry》1998,71(6):2252-2259
Abstract: The diverse physiological actions of galanin are thought to be mediated through activation of galanin receptors (GalRs). We report the genomic and cDNA cloning of a mouse GalR that possesses a genomic structure distinct from that of GalR1 and encodes a functional galanin receptor. The mouse GalR gene consists of two exons separated by a single intron within the protein-coding region. The splicing site for the intron is located at the junction between the third transmembrane domain and the second intracellular loop. The cDNA encodes a 370-amino acid putative G protein-coupled receptor that is markedly different from human GalR1 and rat GalR3 (38 and 57%) but shares high homology with rat GalR2 (94%). In binding studies utilizing membranes from COS-7 cells transfected with mouse GalR2 cDNA, the receptor displayed high affinity ( K D = 0.47 n M ) and saturable binding with 125 I-galanin ( B max = 670 fmol/mg). The radioligand binding can be displaced by galanin and its analogues in a rank order: galanin ⋍ M40 ⋍ M15 ⋍ M35 ⋍ C7 ⋍ galanin (2–29) ⋍ galanin (1–16) ≫ galanin (10–29) ⋍ galanin (3–29), which resembles the pharmacological profile of the rat GalR2. Receptor activation by galanin in COS-7 cells stimulated phosphoinositide metabolism, which was not reversed by pertussis toxin. Thus, the galanin receptor encoded in the cloned mouse GalR gene is the type 2 galanin receptor and is active in both ligand binding and signaling assays. 相似文献
43.
目的:探讨苦参碱拮抗哇巴因诱导的心律失常的作用机制。方法:应用全细胞膜片钳技术记录哇巴因对单个豚鼠心室肌细胞的Na+电流和动作电位时程作用后,观察苦参碱对哇巴因诱导Na+电流和动作电位时程改变的恢复作用。结果:1 5μmol·L-1哇巴因延长APD50从给药前476±40.7 ms增加到744±62.9 ms(n=6,P0.05),APD90从给药前499±84.9 ms增加到775±87.7 ms(n=6,P0.01),100μmol·L-1苦参碱恢复APD50至603±79.0 ms(n=6,P0.05),APD90至630±81.6 ms(n=6,P0.05);2 5μmol·L-1哇巴因可增加钠电流的峰值,在-20 m V电压条件下,5μmol·L-1哇巴因增加INa,由正常-40.9±2.32 p A/p F增加到-55.2±2.26 p A/p F(n=8,P0.05),100μmol·L-1苦参碱减少INa至-34.6±2.14 p A/p F(n=8,P0.05);5μmol·L-1哇巴因右移钠通道的激活曲线,并左移钠通道的失活曲线从而改变通道动力学特性;100μmol·L-1苦参碱可抑制哇巴因诱导的INa的增加,并恢复Na+通道动力学特性接近正常。结论:苦参碱拮抗哇巴因诱导的心律失常机制与其抑制哇巴因诱发细胞水平Na+电流的增加,缩短哇巴因诱发APD的延长有关。 相似文献
44.
Assessment of the potential risks posed by chlorinated solvents in groundwater is the key to establish the extent of the contamination and derive achievable remedial targets should remediation deems necessary. This article first presents the application of the American Society for Testing and Materials (ASTM) Risk Based Corrective Actions (RBCA) Guidance to quantitatively evaluate human health and environmental risk for a former chemical works in Shanghai, China. The observed maximum trichloroethylene (TCE) concentration in groundwater at the site reached 1220 mg/l that exceeded its solubility of 1070 mg/l at 10°C (Soil annual average temperature is 10°C in Shanghai). The maximum concentration for cis-1, 2-DCE (DCE) was also found to be elevated at 264 mg/l. A critical exposure pathway was considered to be indoor vapor intrusion of TCE into the buildings with excess lifetime cancer risk for children being 1.7 × 10?3. This cancer risk exceeded regulatory limits of 1 × 10?4 to 1 × 10?6 for The Netherlands, the United Kingdom, and the United States. The calculated groundwater remedial targets for TCE and DCE are 7 mg/l and 904 mg/l, respectively, in order to protect child residents from inhalation of indoor vapors within the close proximity of the source area. 相似文献
45.
Action potentials induced by electrical stimuli were recorded from the thalli of tfie liverwort, Conocephalum conicum L. An analysis of an equivalent circuit of Conocephalum conicum thallus in situ has shown that the multiphasic time course of extracellular recordings is caused by a branching of extracellular conduction layers and by an overlapping of action currents. As compared to the velocity of excitation propagation without short-circuiting, more than 10 times higher rates of action potential conduction have been recorded when the plants are immersed in a low resistaace solution. Furthermore, simultaneous extra- and intracellular recordings from thalli in situ are presented. 相似文献
46.
Chronic cardiac resynchronization therapy and reverse ventricular remodeling in a model of nonischemic cardiomyopathy 总被引:2,自引:0,他引:2
Nishijima Y Sridhar A Viatchenko-Karpinski S Shaw C Bonagura JD Abraham WT Joshi MS Bauer JA Hamlin RL Györke S Feldman DS Carnes CA 《Life sciences》2007,81(14):1152-1159
While cardiac resynchronization therapy (CRT) has been shown to reduce morbidity and mortality in heart failure (HF) patients, the fundamental mechanisms for the efficacy of CRT are poorly understood. The lack of understanding of these basic mechanisms represents a significant barrier to our understanding of the pathogenesis of HF and potential recovery mechanisms. Our purpose was to determine cellular mechanisms for the observed improvement in chronic HF after CRT. We used a canine model of chronic nonischemic cardiomyopathy. After 15 months, dogs were randomized to continued RV tachypacing (untreated HF) or CRT for an additional 9 months. Six minute walk tests, echocardiograms, and electrocardiograms were done to assess the functional response to therapy. Left ventricular (LV) midmyocardial myocytes were isolated to study electrophysiology and intracellular calcium regulation. Compared to untreated HF, CRT improved HF-induced increases in LV volumes, diameters and mass (p<0.05). CRT reversed HF-induced prolongations in LV myocyte repolarization (p<0.05) and normalized HF-induced depolarization (p<0.03) of the resting membrane potential. CRT improved HF-induced reductions in calcium (p<0.05). CRT did not attenuate the HF-induced increases in LV interstitial fibrosis. Using a translational approach in a chronic HF model, CRT significantly improved LV structure; this was accompanied by improved LV myocyte electrophysiology and calcium regulation. The beneficial effects of CRT may be attributable, in part, to improved LV myocyte function. 相似文献
47.
It is widely accepted that the APD (action potential duration) restitution plays a key role in the initializing and maintaining of the reentry arrhythmias. The Luo-Rudy II models paced with different protocols showed that the current APD had a complex relation with the previous APDs and diastole intervals (DIs). This relation could not be accurately described by a single exponential function. We used an artificial neural network to formularize this relation. The results suggested that back-propagation (BP) network could predict the current APD from the information of the first three previous beats. This would help provide a target for potential anti-arrhythmic therapies. 相似文献
48.
NFATc-mediated gene expression constitutes a critical step during neuronal development and synaptic plasticity. Although considerable information is available regarding the activation and functionality of specific NFATc isoforms, in neurons little is known about how sensitive NFAT nuclear translocation is to specific patterns of electrical activity. Here we used high-speed fluo-4 confocal imaging to monitor action potential (AP)-induced cytosolic Ca2+ transients in rat sympathetic neurons. We have recorded phasic and repetitive AP patterns, and corresponding Ca2+ transients initiated by either long (100-800 ms) current-clamp pulses, or single brief (2 ms) electrical field stimulation. We address the functional consequences of these AP and Ca2+ transient patterns, by using an adenoviral construct to express NFATc1-CFP and evaluate NFATc1-CFP nuclear translocation in response to specific patterns of electrical activity. Ten Hertz trains stimulation induced nuclear translocation of NFATc1, whereas 1 Hz trains did not. However, 1 Hz train stimulation did result in NFATc1 translocation in the presence of 2 mM Ba2+, which inhibits M-currents and promotes repetitive firing and the accompanying small (approximately 0.6 DeltaF/F0) repetitive and summating Ca2+ transients. Our results demonstrate that M-current inhibition-mediated spike frequency facilitation enhances cytosolic Ca2+ signals and NFATc1 nuclear translocation during trains of low frequency electrical stimulation. 相似文献
49.
Prasanna K. Devaraneni Gregory M. Martin Erik M. Olson Qing Zhou Show-Ling Shyng 《The Journal of biological chemistry》2015,290(12):7980-7991
Small molecules that correct protein misfolding and misprocessing defects offer a potential therapy for numerous human diseases. However, mechanisms underlying pharmacological correction of such defects, especially in heteromeric complexes with structurally diverse constituent proteins, are not well understood. Here we investigate how two chemically distinct compounds, glibenclamide and carbamazepine, correct biogenesis defects in ATP-sensitive potassium (KATP) channels composed of sulfonylurea receptor 1 (SUR1) and Kir6.2. We present evidence that despite structural differences, carbamazepine and glibenclamide compete for binding to KATP channels, and both drugs share a binding pocket in SUR1 to exert their effects. Moreover, both compounds engage Kir6.2, in particular the distal N terminus of Kir6.2, which is involved in normal channel biogenesis, for their chaperoning effects on SUR1 mutants. Conversely, both drugs can correct channel biogenesis defects caused by Kir6.2 mutations in a SUR1-dependent manner. Using an unnatural, photocross-linkable amino acid, azidophenylalanine, genetically encoded in Kir6.2, we demonstrate in living cells that both drugs promote interactions between the distal N terminus of Kir6.2 and SUR1. These findings reveal a converging pharmacological chaperoning mechanism wherein glibenclamide and carbamazepine stabilize the heteromeric subunit interface critical for channel biogenesis to overcome defective biogenesis caused by mutations in individual subunits. 相似文献
50.