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Ion Channel Gating (0):
Recent article
Ion Channel Gating
Abstract
Ion channels in cell membranes are targets for a multitude of ligands including naturally occurring toxins, illicit drugs, and medications used to manage pain and treat cardiovascular, neurological, autoimmune, and other health disorders. In the past decade, the x-ray crystallography...
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PMID: 21961291
PDF is available here.
PDF is available here.
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Abstract
We describe separate lines with human α7 and human α4β2 nicotinic acetylcholine receptors, mouse 5-HT(3A) serotonin receptors and a chimera of human α7/mouse 5-HT(3A) receptors. Complete concentration-response curves for agonists and Schild plots of antagonists were generated from these sensors...
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PMID: 21305050
PDF is available here.
PDF is available here.
Abstract
We introduce a biosynthetic system that permits studies of both channel activity in single cells and electrical conduction in multicellular networks. We convert unexcitable somatic cells into an autonomous source of electrically excitable and conducting cells by stably expressing only three membrane...
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PMID: 21556054
PDF is available here.
PDF is available here.
Abstract
We recently reported that endogenous SNAP-25 negatively regulates VGCC activity in glutamatergic neurons from rat hippocampal cultures by shifting the voltage-dependence of inactivation of the predominant P/Q-type channel current in these cells. In the present study, we extend these findings by inve...
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PMID: 21558797
PDF is available here.
PDF is available here.
Abstract
We evaluate the influence of spontaneous GABAergic synaptic activity on the timing of action potentials in Layer 2/3 pyramidal neurones in acute brain slices from the somatosensory cortex of young rats. Somatic dynamic current injection to mimic synaptic input events was employed, together with a si...
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PMID: 21789249
PDF is available here.
PDF is available here.
Abstract
We studied Xenopus laevis neural crest, an embryonic stem cell population that gives rise to many cell types, including melanocytes, and contributes to the morphogenesis of the face, heart and other complex structures. To investigate how depolarization of transmembrane potential of cells in the neur...
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PMID: 20959630
PDF is available here.
PDF is available here.
Abstract
We focus on Nedd4 and Nedd4-2 ubiquitin ligases and the mechanisms by which they regulate voltage-gated ion channels and describe a novel paradigm on the mechanisms that underpin aberrant ion channel function in neurological disorders....
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PMID: 21057195
PDF is available here.
PDF is available here.
Abstract
We have accomplished thermodynamic analysis of mouse TREK-1 gating and functional testing of several deletion mutants. The predicted increase of the channel in-plane area (ΔA) of ~5 nm(2) in models was supported by the experimental ΔA of ~4 nm(2) derived from the slope of open probability versus m...
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PMID: 21057213
PDF is available here.
PDF is available here.
Journal of Biological Chemistry (285)43 2010
Abstract
We examine the effect of the β3-subunit on the gating behavior of Na(v)1.3 using whole cell patch clamp electrophysiology in HEK-293 cells. We show that β3 depolarizes the voltage sensitivity of Na(v)1.3 activation and inactivation and induces biphasic components of the inactivation curve. We dete...
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PMID: 20675377
PDF is available here.
PDF is available here.
Abstract
We report that activation of dopamine D1 receptors in dentate granule cells (DGCs) can preferentially increase dendritic excitability to both high-frequency afferent activity and high-frequency trains of backpropagating action potentials. Using whole-cell patch clamp recordings, calcium imaging, and...
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PMID: 20921404
PDF is available here.
PDF is available here.
Biochemical Journal (431)2 2010
Abstract
We studied the efficacy and selectivity of BmK I to three neuronal VGSCs co-expressed with the auxiliary β1 subunit in Xenopus oocytes. Results revealed that BmK I induced a large increase in both transient and persistent currents in mNav1.6α/β1 (where m indicates mouse), which correlated with a...
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PMID: 20678086
PDF is available here.
PDF is available here.
Abstract
Cystic fibrosis transmembrane conductance regulator (CFTR) anion channel, a member of ABC transporter superfamily, gates following ATP-dependent conformational changes of the nucleotide binding domains (NBD). Reflecting the hundreds of milliseconds duration of the channel open state corresponding to...
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PMID: 20628841
PDF is available here.
PDF is available here.
Abstract
We aimed to study kinetics of modulation by intracellular Mg(2+) of cardiac gap junction (Mg(2+) gate). Paired myocytes of guinea-pig ventricle were superfused with solutions containing various concentrations of Mg(2+). In order to rapidly apply Mg(2+) to one aspect of the gap junction, the non-junc...
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PMID: 20553744
PDF is available here.
PDF is available here.
Biophysical Journal (99)4 2010
Abstract
We found that series connection does not lead to a single minimum of stiffness with respect to hair bundle displacement unless the minimum is above a certain positive value. Thus, negative stiffness must appear in pairs in the displacement axis. In contrast, parallel connection of the two channels p...
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PMID: 20712985
PDF is available here.
PDF is available here.
Abstract
We thoroughly analyzed the bone phenotype of Trpv6(-/-) mice receiving a normal (approximately 1%) or low (approximately 0.02%) calcium diet from weaning onwards using micro-computed tomography, histomorphometry and serum parameters. When dietary supply of calcium is normal, Trpv6 inactivation did n...
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PMID: 20399919
PDF is available here.
PDF is available here.
Abstract
We explored the potential role of transient receptor potential (TRP) channels in this process. Previously, we observed that after metabolism AEA and arachidonic acid (ArA) can be recycled into new endocannabinoid molecules. Consistent with these previous findings, we found that Cath.a differentiated...
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PMID: 20466028
PDF is available here.
PDF is available here.
Abstract
We show that high-voltage activated Ca(2+) channels are regulated by membrane phosphatidylinositol 4,5-bisphosphate (PIP(2)) with different sensitivities. Plasma membrane PIP(2) depletion by rapamycin-induced translocation of an inositol lipid 5-phosphatase or by a voltage-sensitive 5-phosphatase (V...
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PMID: 20670831
PDF is available here.
PDF is available here.
Abstract
We established a compendium of functional correlates between changes in membrane potential and the dynamic discharge properties of these sensory neurons as a result of the controlled recruitment of I(h) using the current clamp technique. 3. Two robust responses were observed in response to hyperpola...
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PMID: 20456426
PDF is available here.
PDF is available here.
Biochimica et Biophysica Acta (1798)9 2010
Abstract
We now show that reduced permeability of one does not protect the intracellular parasite from the other. Leupeptin accumulation in the blasticidin S-resistant mutant was relatively preserved, consistent with retained in vitro susceptibility to leupeptin. Subsequent in vitro selection with both toxin...
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PMID: 20451492
PDF is available here.
PDF is available here.
Abstract
We present evidence that in non-excitable LNCaP prostate cancer cells, BK channels can be activated at negative voltages without rises in [Ca(2+)](i) through their complex with an auxiliary protein, leucine-rich repeat (LRR)-containing protein 26 (LRRC26). LRRC26 modulates the gating of a BK channel...
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PMID: 20613726
PDF is available here.
PDF is available here.
Abstract
We show that full ligand-induced activation appears already with only two ligands bound to the tetrameric channel. Kinetic analysis of channel activation and ligand binding suggests direct interaction between the voltage sensor and the cyclic nucleotide-binding domain, bypassing the pore. By exploit...
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PMID: 20624593
PDF is available here.
PDF is available here.
Journal of Biological Chemistry (285)29 2010
Abstract
We show that mutations in the C terminus of the first nucleotide binding domain comprising the latest beta strands (beta(c)5 and beta(c)6) influence the trafficking, channel activity, and pharmacology of CFTR. We mutated CFTR amino acids located in the beta(c)5-beta(c)6 hairpin, within the beta(c)5...
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PMID: 20435887
PDF is available here.
PDF is available here.
Journal of Biological Chemistry (285)29 2010
Abstract
We found that in species with high baseline plasma pH, e.g. frog, shark, and fish, ASIC1 has high proton affinity compared with the mammalian channel. The beta1-beta2 linker in the extracellular domain, specifically by the substitution M85L, determines the interspecies differences in proton affiniti...
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PMID: 20479002
PDF is available here.
PDF is available here.
Journal of Biological Chemistry (285)29 2010
Abstract
We showed that the inhibitory efficacy of the ribbon isomer of AuIB is limited to approximately 50%. The maximal inhibition was stoichiometry-dependent because altering alpha3:beta4 RNA injection ratios either increased AuIB(ribbon) efficacy (10alpha:1beta) or completely abolished blockade (1alpha:1...
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PMID: 20466726
PDF is available here.
PDF is available here.
Journal of Biological Chemistry (285)29 2010
Abstract
We demonstrate, using a combination of protein chemistry and mass spectrometry, the occurrence of three O-acylated polypeptides in Corynebacterium glutamicum, PorA, PorH, and an unknown small protein. The three polypeptides are O-substituted by mycolic acids, long chain alpha-alkyl and beta-hydroxy...
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PMID: 20508265
PDF is available here.
PDF is available here.
Abstract
Abstract
We determined the x-ray structure of the human BK Ca2+ gating apparatus at a resolution of 3.0 angstroms and deduced its tetrameric assembly by solving a 6 angstrom resolution structure of a Na+-activated homolog. Two tandem C-terminal regulator of K+ conductance (RCK) domains from each of four chan...
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PMID: 20508092
PDF is available here.
PDF is available here.
Abstract
We identify the mechanistic principles by which movements on the inner bundle gate trigger conformational changes at the selectivity filter, leading to the non-conductive C-type inactivated state. Analysis of a series of KcsA open structures suggests that, as a consequence of the hinge-bending and r...
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PMID: 20613845
PDF is available here.
PDF is available here.
Abstract
We report the crystal structure of the Streptomyces lividans K(+) channel KcsA in its open-inactivated conformation and investigate the mechanism of C-type inactivation gating at the selectivity filter from channels 'trapped' in a series of partially open conformations. Five conformer classes were i...
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PMID: 20613835
PDF is available here.
PDF is available here.
Abstract
We introduce an integrate-and-fire spiking neuron model that includes a biophysically realistic model of I(T). We briefly review the subthreshold bifurcation diagram of this model with constant current injection before moving on to consider its response to periodic forcing. Direct numerical simulati...
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PMID: 20866665
PDF is available here.
PDF is available here.
Nature Neuroscience (13)7 2010
Abstract
We found that FMRP binds to the C terminus of the Slack sodium-activated potassium channel to activate the channel in mice. Our findings suggest that Slack activity provides a link between patterns of neuronal firing and changes in protein translation....
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PMID: 20512134
PDF is available here.
PDF is available here.
Abstract
We show here that the ASIC1 ortholog of an early vertebrate, lamprey ASIC1, does not respond to protons; however, only two amino acid substitutions for the corresponding ones in rat ASIC1, Q77L and T85L, convert lamprey ASIC1 into a highly sensitive proton-activated channel with apparent H(+) affini...
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PMID: 20427715
PDF is available here.
PDF is available here.
Abstract
We identified the voltage-gated Kv1.3 channel in the inner medulla of the rat kidney (Escobar LI, Martínez-Téllez JC, Salas M, Castilla SA, Carrisoza R, Tapia D, Vázquez M, Bargas J, Bolívar JJ. Am J Physiol Cell Physiol 286: C965-C974, 2004). To examine the role of Kv1.3 in the renal regulation...
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PMID: 20427469
PDF is available here.
PDF is available here.
Abstract
We examined the effects of cell-permeable C(6)-ceramide on HERG potassium channels stably expressed in HEK-293 cells. C(6)-ceramide (10 microM) reversibly inhibited HERG channel current (I(HERG)) by 36 +/- 5%. Kinetically, ceramide induced a significant hyperpolarizing shift in the current-voltage r...
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PMID: 20375276
PDF is available here.
PDF is available here.
Abstract
Store-operated Ca(2+) entry (SOCE) is an important mechanism in virtually all cells. In adult skeletal muscle, this mechanism is highly specialized for the rapid delivery of Ca(2+) from the transverse tubule into the junctional cleft during periods of depleting Ca(2+) release. In dystrophic muscle f...
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PMID: 20427714
PDF is available here.
PDF is available here.
Abstract
We tested a hypothesis that lubiprostone can reverse the constipating action of morphine and investigated the mechanism of action. Short-circuit current (Isc) was recorded in Ussing chambers as a marker for chloride secretion during pharmacological interactions between morphine and lubiprostone. Mea...
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PMID: 20406855
PDF is available here.
PDF is available here.
Abstract
The present experiments investigated whether endothelium-derived mediators modulate the effect of natriuretic peptides in porcine coronary arteries. Rings with and without endothelium were suspended in organ chambers for isometric tension recording. Concentration-relaxation curves to...
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PMID: 20332186
PDF is available here.
PDF is available here.
Abstract
We report here electrical measurements to examine how Na/K pump interactions with extracellular Na ions are influenced by C-terminal truncations. We deleted the last two (YY) or five (KESYY) residues in Xenopus laevis alpha1 Na/K pumps made ouabain resistant by either of two kinds of point mutations...
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PMID: 20548052
PDF is available here.
PDF is available here.
Abstract
We investigated the identity and the pH-dependent function of the apical H(+) channel in the airway epithelium. In pH stat recordings of confluent JME airway epithelia in Ussing chambers, Zn-sensitive acid secretion was activated at a mucosal threshold pH of approximately 7, above which it increased...
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PMID: 20548053
PDF is available here.
PDF is available here.
Abstract
We analyze how the characteristics of spontaneous and triggered calcium sparks are related to cardiac ryanodine receptor (RYR) gating. We show that the frequency of spontaneous sparks and the probability distribution of calcium release flux quanta of triggered sparks correspond quantitatively to pre...
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PMID: 20548054
PDF is available here.
PDF is available here.
Abstract
We examined two such mutations, A40V and G45E, which are positioned near the TM1/E1 boundary and are associated with keratitis ichthyosis deafness (KID) syndrome. Both of these mutants have been reported to form hemichannels that open aberrantly, leading to "leaky" cell membranes. Here, we quantifie...
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PMID: 20584891
PDF is available here.
PDF is available here.
Abstract
The Kv1.2 channel, with its high resolution crystal structure, provides an ideal model for investigating conformational changes associated with channel gating, and fluorescent probes attached at the extracellular end of S4 are a powerful way to gain a more complete understanding of t...
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PMID: 20584892
PDF is available here.
PDF is available here.
Abstract
We show that a cytosolic motif immediately following the activation gate S6 helix, known as the AC region, mediates the allosteric coupling between Ca(2+) binding and channel opening. The GEPD mutation inside the AC region increases BK channel activity by enhancing this allosteric coupling. We found...
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PMID: 20620873
PDF is available here.
PDF is available here.
Journal of Neuroscience (30)25 2010
Abstract
We developed a nominal biophysical model of the crustacean cardiac ganglion using biological data. Predictions from the nominal model showed that coregulation of ionic currents may preserve the key characteristics of motor neuron activity. We then developed a methodology of sampling a multidimension...
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PMID: 20573909
PDF is available here.
PDF is available here.
Journal of Neuroscience (30)25 2010
Abstract
We have examined the idea that the presence of beta subunits also modifies the pharmacological properties of the Na(+) channel complex using mice lacking either the beta(1) (Scn1b) or beta(2) (Scn2b) subunit. Classical effects of the anticonvulsant carbamazepine (CBZ), such as the use-dependent redu...
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PMID: 20573896
PDF is available here.
PDF is available here.
Biochemistry (Washington) (49)23 2010
Abstract
We considered that protons may traverse a separate pathway but were unable to find any evidence for one. Manipulations that interfere with ionic conduction, such as replacing some of the water in the pore with a nonelectrolyte, reduce the proton current along with the ionic current. Lipids have been...
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PMID: 20459128
PDF is available here.
PDF is available here.
Abstract
We investigated the voltage-dependence of the gating kinetics of unitary LCCs, with a physiologic concentration of Ca(2+) ions permeating the channel. Unitary LCC currents were recorded with 2mM external Ca(2+) ions (in the absence of LCC agonists), using cell-attached patches on K-depolarized adult...
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PMID: 20457123
PDF is available here.
PDF is available here.
Abstract
Mitochondrial porin forms an aqueous pore in the outer membrane, through which selective passage of small metabolites and ions occurs, thereby regulating both mitochondrial function and cellular respiration. Investigations of the structure and function of porin have been performed with whole mitocho...
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PMID: 20555384
PDF is available here.
PDF is available here.
Abstract
We conclude that I(NCX) is functionally expressed in developing ventricular hESC-CMs and contributes to their excitation-contraction coupling....
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PMID: 19719399
PDF is available here.
PDF is available here.
Neuroscience (167)4 2010
Abstract
We used multicompartment neuron models to identify ranges of active and passive cell properties that are necessary to reproduce the sharp AP onset in the invasion scenario. Results of our simulations show that AP initiation in the axon is a necessary but not a sufficient condition for the sharp onse...
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PMID: 20211703
PDF is available here.
PDF is available here.
Neuroscience (167)4 2010
Abstract
We study the expression and localization of BK(Ca) channels and CGRP in the rat trigeminal ganglion (TG) and the trigeminal nucleus caudalis (TNC) as these structures are involved in migraine pain. Also the effect of the BK(Ca) channel blocker iberiotoxin and the BK(Ca) channel opener NS11021 on CGR...
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PMID: 20211697
PDF is available here.
PDF is available here.
Neuropharmacology (58)8 2010
Abstract
We report here that genistein inhibits N-methyl-d-aspartate (NMDA) receptors through a direct effect. Whole-cell NMDA-activated current was recorded in native receptors from mouse hippocampal slice culture and rat recombinant NR1aNR2A and NR1aNR2B receptors transiently expressed in HEK293 cells. Ext...
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PMID: 20303997
PDF is available here.
PDF is available here.
Abstract
We generated mice with knockin mutations of alpha(1)1.2 S1512 and S1570 phosphorylation sites [sine facilitation (SF) mice]. Homocygote SF mice were viable and reproduced in a Mendelian ratio. Voltage-dependent facilitation in ventricular cardiomyocytes carrying the SF mutation was decreased from 1....
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PMID: 20479240
PDF is available here.
PDF is available here.
Journal of Physiology (588)Pt 11 2010
Abstract
We propose a unified loss-of-function hypothesis for the spectrum of epilepsy syndromes caused by genetic changes in NaV1.1 channels, in which mild impairment predisposes to febrile seizures, intermediate impairment leads to GEFS+ epilepsy, and severe or complete loss of function leads to the intrac...
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PMID: 20194124
PDF is available here.
PDF is available here.
Journal of Physiology (588)Pt 11 2010
Abstract
Journal of Physiology (588)Pt 11 2010
Abstract
We summarise the recent advances in the understanding of the molecular pathophysiology of hypoPP and consider how these may relate to the reported beneficial effects of acetazolamide. We also consider potential areas for future therapeutic development....
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PMID: 20123788
PDF is available here.
PDF is available here.
Journal of Physiology (588)Pt 11 2010
Abstract
Journal of Physiology (588)Pt 11 2010
Abstract
Mutations of voltage-gated ion channels cause several channelopathies of skeletal muscle, which present clinically with myotonia, periodic paralysis, or a combination of both. Expression studies have revealed both loss-of-function and gain-of-function defects for the currents passed by mutant channe...
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PMID: 20156847
PDF is available here.
PDF is available here.
Journal of Physiology (588)Pt 11 2010
Abstract
We compare a patch-clamp robot using planar-chip technology with human patch-clamp in a functional assessment of a previously undescribed Nav1.7 sodium channel mutation, S211P, which causes erythromelalgia. This robotic patch-clamp device can increase throughput (the number of cells analysed per day...
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PMID: 20123784
PDF is available here.
PDF is available here.
Journal of Neuroscience (30)21 2010
Abstract
Retinal ganglion cells (RGCs) are the output cells of the retina; they convert synaptic input into spike output that carries visual information to the brain. Synaptic inputs are received, integrated and communicated to the spike initiation zone of the axon by dendrites whose properties are poorly un...
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PMID: 20505081
PDF is available here.
PDF is available here.