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1.
Voltage-Gated calcium channels and nonvoltage-gated calcium uptake pathways in the rat incisor odontoblast plasma membrane 总被引:4,自引:1,他引:3
Odontoblasts participate actively in the transport and accumulation of Ca2+ ions to the mineralization front during dentinogenesis. These cells are known to carry membrane-bound ATP-driven pumps and
Na+/Ca2+ antiports for Ca2+ extrusion, but little is known about Ca2+ influx mechanisms into these cells. It has been shown that the administration of Ca2+ channel blockers in vivo strongly impairs Ca2+ uptake in the mineral phase during dentinogenesis in the rat; the present in vitro study is aimed at further elucidating
odontoblast Ca2+ uptake mechanisms. Dissected rat incisor odontoblasts exhibited a pronounced fluorescence when incubated with a fluorescently-labeled
(STBodipy) dihydropyridine, which is specific for voltage-gated Ca2+ channels of the L-type, and this binding was competitively abolished by nifedipine. As assayed by fluorescence spectrometry,
odontoblast Ca2+ uptake was enhanced by the agonistic dihydropyridine BAYK-8644 (5 μM) as well as by plasma membrane depolarization in a high
K+ (120 mM) medium. The Ca2+ uptake after depolarization was impaired by nifedipine (5 μM). When treated with the Ca2+-ATPase inhibitor cyclopiazonic acid (CPA; 10 μM), a nonvoltage-gated uptake of 45Ca2+ was identified. This uptake was not influenced by nifedipine (20 μM) but was impaired by lanthanum ions (200 μM). A nonvoltage-gated
uptake of Mn2+ into CPA-treated cells could be traced using the fura-2 quenching technique. This CPA-induced Ca2+ flux was not caused by an alteration of the plasma membrane potential, as assayed with di-8-ANEPPS. The results demonstrate
that Ca2+ flux into dentinogenically active odontoblasts occurs through voltage-gated Ca2+ channels of the L-type and by nonvoltage-gated, agonist-sensitive Ca2+ uptake pathways.
Received: 6 November 1995 / Accepted: 21 February 1996 相似文献
2.
Paul McIntosh Andrew P. Southan Sobia Akhtar Christina Sidera Yuri Ushkaryov J. Oliver Dolly B. Robertson 《Pflügers Archiv : European journal of physiology》1997,435(1):43-54
We have examined the effects of co-expression of Kvβ1.1 and Kvβ2.1 subunits on the gating of rat brain Kv1.4 channels, expressed
in Xenopus oocytes. Expression of Kv1.4 subunits alone produced a rapidly inactivating ”A” type current, which activated at potentials
beyond –60 mV in a solution containing high levels of rubidium. Current activation curves obtained from tail current measurements
were fitted with a Boltzmann function, with V
1/2 = –47 mV and k = 10 mV. Neither the Kvβ1.1 nor Kvβ2.1 subunits altered the voltage dependence of activation. Both subunits accelerated the
activation time constant of Kv1.4, without affecting its voltage dependence. Surprisingly, the Kvβ2.1 subunit, which lacks
an N-terminal inactivation domain, was almost as effective as the Kvβ1.1 subunit in speeding up Kv1.4. Steady-state inactivation
of Kv1.4 was unchanged upon co-expression with either Kvβ1.1 or Kvβ2.1 subunits. Kv1.4 recovered from inactivation with two
time constants; apart from an ≈ 50% lengthening of the slow time constant with a high Kvβ2.1 injection ratio, neither time
constant was altered by either the Kvβ1.1 or Kvβ2.1 subunits, suggesting little interaction with recovery from C-type inactivation.
Clearly, β subunits have the potential to modify the gating of Kv1.4 channels in the brain more subtly than has been suggested
previously.
Received: 17 March 1997 / Accepted: 30 June 1997 相似文献
3.
目的: 探讨在不同钙离子浓度下电压门控钠离子通道(NaV)1.2与钙调蛋白(CaM)的结合,并分析CaM的钙离子结合位点突变后与NaV1.2结合能力的变化。方法: 应用PCR技术构建NaV1.2蛋白片段异亮氨酸-谷胺酰胺(IQ)基序的cDNA,采用QIAGEN点突变技术构建CaM突变体(CaM12、CaM34、CaM1234),应用牵出(pull-down)试验技术检测有钙(100 nmol/L钙离子浓度)和无钙条件下NaV1.2 IQ与CaM及其突变体(CaM12、CaM34、CaM1234)的结合情况。结果: CaM与NaV1.2 IQ在无钙和有钙情况下均可互相结合,而单独重组谷胱甘肽-S-转移酶(GST)不具有与CaM结合的能力。无钙条件下CaM与NaV1.2 IQ的结合量大于有钙条件下两者的结合量(P < 0.05);无钙条件下,CaM野生型与NaV1.2 IQ结合量大于CaM突变体与NaV1.2 IQ的结合量,其中CaM1234的结合能力在三个突变体中最弱(P < 0.05)。结论: CaM及其突变体对NaV1.2 IQ的结合具有钙离子依赖性,这一CaM调控NaV1.2新机制为离子通道疾病研究提供了一定依据。 相似文献
4.
PurposeLacosamide (LCM) and carbamazepine (CBZ) are antiepileptic drugs both acting on neuronal voltage-gated sodium channels. Patch-clamp studies demonstrated significant differences in how LCM and CBZ affect neuronal membrane excitability. Despite valuable information patch-clamp studies provide, they also comprise some constraints. For example, little is known about effects of LCM on intracortical synaptic excitability. In contrast, transcranial magnetic stimulation (TMS) can describe drug-induced changes at the system level of the human cerebral cortex.MethodsThe present study was designed to explore dose-depended effects of LCM and effects of CBZ on motor cortex excitability with TMS in a randomized, double-blind, placebo-controlled crossover trial in healthy human subjects. Subjects received 600 mg CBZ, 200 mg LCM, 400 mg LCM or placebo preceding TMS measurements.ResultsCompared to placebo, TMS motor thresholds were significantly increased after carbamazepine and lacosamide, with a trend for a dose dependent effect of lacosamide. Both, carbamazepine and lacosamide did not affect TMS parameters of intracortical synaptic excitability.ConclusionsTMS measurements suggest that lacosamide and carbamazepine predominantly act on neuronal membrane excitability. 相似文献
5.
6.
癫痫是一类抽搐相关性神经系统疾病,其发病机制复杂,临床治疗困难,严重影响人类的健康。随着分子遗传学和药理学的发展,癫痫的发病机制也取得了很大的进展。大量的研究表明,电压依赖性离子通道在癫痫的发病中发挥着重要的作用。现从分子水平对电压依赖性钠离子通道与癫痫的相关性及其亚基的相互作用方面进行综述。 相似文献
7.
Johnson JD VanGoor F Jobin RM Wong CJ Goldberg JI Chang JP 《Molecular and cellular endocrinology》2000,170(1-2):15-29
Ca2+ signals regulate many cellular functions, including hormone secretion. Agonist-specific Ca2+ signaling may arise from the differential mobilization of multiple Ca2+ stores. Although they act through the same receptor subtype, two gonadotropin-releasing hormones (sGnRH and cGnRH-II) generate quantifiably different Ca2+ signals in goldfish gonadotropes, suggesting that their Ca2+-dependent signaling cascades may differ. We combined electrophysiology, Ca2+ imaging, and radioimmunoassay detection of gonadotropin (GTH-II) secretion to determine the role of intracellular Ca2+ stores in GnRH-stimulated exocytosis. Our findings suggest that voltage-gated Ca2+ channels do not mediate acute GnRH-signaling. Instead, both sGnRH- and cGnRH-II-stimulated GTH-II releases are dependent on Ca2+ mobilized from TMB–8/CPA-sensitive compartments. However, sGnRH, but not cGnRH-II, utilizes intracellular stores sensitive to caffeine and xestospongin C. We also identified a homeostatic mechanism where reduced extracellular Ca2+ availability increase GTH-II release by mobilizing Ca2+ stores. Our results are the first to suggest that several classes of intracellular Ca2+ stores differentially participate in agonist signaling and homeostasis in gonadotropes. 相似文献
8.
Naoual Oukkache Jean-Pierre Rosso Meriem Alami Norredine Ghalim Rachid Sa?le Mohammed Hassar Pierre E Bougis Marie-France Martin-Eauclaire 《Toxicon》2008,51(5):835-852
Scorpion venoms are very complex mixtures of molecules, most of which are peptides displaying different kinds of biological activity. Indeed, these peptides specifically bind to a variety of pharmacological targets, in particular ionic channels located in prey tissues, resulting in neurotoxic effects. Toxins modulating Na+, K+, Ca2+ and Cl(-) currents have been described in scorpion venoms. In this work, we have used several specific antibodies raised against the most lethal scorpion toxins already described to screen the Moroccan scorpion Androctonus mauretanicus mauretanicus venom in order to characterize new compounds. This immunological screening was also implemented by toxicity tests in mice and with mass spectrometry study, providing new informations on the molecular composition of this venom. In fine, we were able to determine the molecular masses of 70-80 different compounds. According to the immunological data obtained, many toxins cross-react with three sera raised against the most lethal alpha-toxins found in North African scorpion venoms, but not at all with those raised against the main beta-toxins from South and North American venoms. Some of the previously described toxins from Androctonus mauretanicus mauretanicus venom could thus be detected by combining immunological tests, toxicity in mice and molecular masses. Among these toxins, one of them, which showed a mild cross-reaction with the serum raised against AaH I (a highly potent toxin from the venom of Androctonus australis), was identified as Amm III and fully sequenced. 相似文献
9.
The critical role that ether-à-go-go-related gene (erg) K(+) channels play in mating in Caenorhabditis elegans, neuronal seizures in Drosophila and cardiac action potential repolarization in humans has been well documented. Three erg genes (erg1, erg2 and erg3) have been identified and characterized. A structurally diverse number of compounds block these channels, but do not display specificity among the different channel isoforms. In this review we describe the blocking properties of several peptides, purified from scorpion, sea anemone and spider venoms, which are selective for certain members of the ERG family of channels. These peptides do not behave as classical pore blockers and appear to modify the gating properties of the channel. Genomic studies predict the existence of many other novel peptides with the potential of being more selective for ERG channels than those discussed here. 相似文献
10.
Taste bud cells (TBCs) on soft palates differ from those on tongues in innervation and chemosensitivity. We investigated voltage-gated channels involved in the taste responses of TBCs on mouse soft palates under in-situ tight-seal voltage/current-clamp conditions. Under the cell-attached mode, TBCs spontaneously fired action currents, which were blocked by application of 1 microM TTX to TBC basolateral membranes. Firing frequencies increased in response to taste substances applied to TBC receptor membranes. Under the whole-cell clamp mode, as expected, TBCs produced various voltage-gated currents such as TTX-sensitive Na+ currents (INa), outward currents (Iout) including TEA-sensitive and insensitive currents, inward rectifier K+ currents (Iir), and Ca2+ currents including T-type, P/Q-type, and L-type Ca2+ currents. We classified TBCs into three types based on the magnitude of their voltage-gated Na+ currents and membrane capacitance. HEX type (60% of TBCs examined) was significantly larger in Na+ current magnitude and smaller in membrane capacitance than LEX type (23%). NEX type (17%) had no Na+ currents. HEX type was equally distributed within single taste buds, while LEX type was centrally distributed, and NEX type was peripherally distributed. There were correlations between these electrophysiological cell types and morphological cell types determined by three-dimensional reconstruction. The present results show that soft palate taste buds contain TBCs with different electrophysiological properties, and suggest that their co-operation is required in taste transduction. 相似文献