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Voltage clamp

Fredrik Elinder, Michael Madeja, Hugo Zeberg, Peter Århem
The transmembrane voltage needed to open different voltage-gated K (Kv) channels differs by up to 50 mV from each other. In this study we test the hypothesis that the channels' voltage dependences to a large extent are set by charged amino-acid residues of the extracellular linkers of the Kv channels, which electrostatically affect the charged amino-acid residues of the voltage sensor S4. Extracellular cations shift the conductance-versus-voltage curve, G(V), by interfering with these extracellular charges...
October 18, 2016: Biophysical Journal
Diego Dal Ben, Anna Marchenkova, Ajiroghene Thomas, Catia Lambertucci, Andrea Spinaci, Gabriella Marucci, Andrea Nistri, Rosaria Volpini
Blocking membrane currents evoked by the activation of purinergic P2X3 receptors localized on nociceptive neurons represents a promising strategy for the development of agents useful for the treatment of chronic pain conditions. Among compounds endowed with such antagonistic action, 2',3'-O-(2,4,6-trinitrophenyl)-ATP (TNP-ATP) is an ATP analogue, whose inhibitory activity on P2X receptors has been previously reported. Based on the results of molecular modelling studies performed with homology models of the P2X3 receptor, novel adenosine nucleotide analogues bearing cycloalkyl or arylalkyl substituents replacing the trinitrophenyl moiety of TNP-ATP were designed and synthesized...
October 18, 2016: Purinergic Signalling
In-Sik Kang, Jin-Hwa Cho, In-Sun Choi, Do-Yeon Kim, Il-Sung Jang
Cell bodies of trigeminal mesencephalic nucleus (Vmes) neurons are located within the central nervous system, and therefore, peripheral as well as central acidosis can modulate the excitability of Vmes neurons. Here, we report the effect of acidic pH on voltage-gated Na channels in acutely isolated rat Vmes neurons using a conventional whole-cell patch clamp technique. Acidic pH (pH 6.0) slightly but significantly shifted both the activation and steady-state fast inactivation relationships toward depolarized potentials...
October 14, 2016: Neuroreport
Anahita Nourmahnad, Alex T Stern, Mayo Hotta, Deirdre S Stewart, Alexis M Ziemba, Andrea Szabo, Stuart A Forman
BACKGROUND: γ-Aminobutyric acid type A (GABAA) receptors mediate important effects of intravenous general anesthetics. Photolabel derivatives of etomidate, propofol, barbiturates, and a neurosteroid get incorporated in GABAA receptor transmembrane helices M1 and M3 adjacent to intersubunit pockets. However, photolabels have not been consistently targeted at heteromeric αβγ receptors and do not form adducts with all contact residues. Complementary approaches may further define anesthetic sites in typical GABAA receptors...
October 7, 2016: Anesthesiology
Neil C Ford, Mark L Baccei
Spinal lamina I projection neurons serve as a major conduit by which noxious stimuli detected in the periphery are transmitted to nociceptive circuits in the brain, including the parabrachial nucleus (PB) and the periaqueductal gray (PAG). While neonatal spino-PB neurons are more than twice as likely to exhibit spontaneous activity compared to spino-PAG neurons, the underlying mechanisms remain unclear since nothing is known about the voltage-independent (i.e. 'leak') ion channels expressed by these distinct populations during early life...
October 14, 2016: Neuroscience
Richard A Gray, Pras Pathmanathan
Elucidating the underlying mechanisms of fatal cardiac arrhythmias requires a tight integration of electrophysiological experiments, models, and theory. Existing models of transmembrane action potential (AP) are complex (resulting in over parameterization) and varied (leading to dissimilar predictions). Thus, simpler models are needed to elucidate the "minimal physiological requirements" to reproduce significant observable phenomena using as few parameters as possible. Moreover, models have been derived from experimental studies from a variety of species under a range of environmental conditions (for example, all existing rabbit AP models incorporate a formulation of the rapid sodium current, INa, based on 30 year old data from chick embryo cell aggregates)...
October 2016: PLoS Computational Biology
Manuel Sánchez, Lorena Suárez, Begoña Cantabrana, Javier Bordallo
Estrogens facilitate prolactin (PRL) secretion acting on pituitary cells. In GH3 cells, estradiol induces acute action potentials and oscillations of intracellular Ca(2+) associated with the secretagogue function. Estradiol modulates several ion channels which may affect the action potential rate and the release of PRL in lactotroph cells, which might depend on its concentration. The aims were to characterize the acute effect of supraphysiological concentrations of estradiol on Ca(2+) and noninactivating K(+) currents and measure the effect on the spontaneous action potentials and PRL release in the somatolactotroph cell line, GH3...
October 17, 2016: Naunyn-Schmiedeberg's Archives of Pharmacology
Keisuke Kaneko, Yuko Koyanagi, Yoshiyuki Oi, Masayuki Kobayashi
Propofol is a major intravenous anesthetic that facilitates GABAA receptor-mediated inhibitory synaptic currents and modulates Ih, K(+), and voltage-gated Na(+) currents. This propofol-induced modulation of ionic currents changes intrinsic membrane properties and repetitive spike firing in cortical pyramidal neurons. However, it has been unknown whether propofol modulates these electrophysiological properties in GABAergic neurons, which express these ion channels at different levels. This study examined whether pyramidal and GABAergic neuronal properties are differentially modulated by propofol in the rat insular cortical slice preparation...
October 13, 2016: Neuroscience
Jingying Gao, Tao Bai, Lele Ren, Yaqin Ding, Xiangqin Zhong, Hui Wang, Yangyan Guo, Jie Li, Yunfeng Liu, Yi Zhang
Uncarboxylated osteocalcin, a bone matrix protein, has been proposed to regulate glucose metabolism by increasing insulin secretion, improving insulin sensitivity and stimulating β cell proliferation. Our previous study also indicated that uncarboxylated osteocalcin stimulates insulin secretion by inhibiting voltage-gated potassium (KV) channels. The goal of this study is to further investigate the underlying mechanisms for the regulation of Kv channels and insulin secretion by uncarboxylated osteocalcin. Insulin secretion and Kv channel currents were examined by radioimmunoassay and patch-clamp technique, respectively...
October 13, 2016: Peptides
Nan Zhang, Shengchang Yang, Chang Wang, Jianghua Zhang, Lifang Huo, Yiru Cheng, Chuan Wang, Zhanfeng Jia, Leiming Ren, Lin Kang, Wei Zhang
Alzheimer's disease (AD) and type II diabetes mellitus (DM2) are the most common aging-related diseases and are characterized by β-amyloid and amylin accumulation, respectively. Multiple studies have indicated a strong correlation between these two diseases. Amylin oligomerization in the brain appears to be a novel risk factor for developing AD. Although amylin aggregation has been demonstrated to induce cytotoxicity in neurons through altering Ca(2+) homeostasis, the underlying mechanisms have not been fully explored...
October 12, 2016: Neuropharmacology
Yu Chen, Xiaojing Mu, Tao Wang, Weiwei Ren, Ya Yang, Zhong Lin Wang, Chengliang Sun, Alex Yuandong Gu
Here, we report a stable and predictable aero-elastic motion in the flow-driven energy harvester, which is different from flapping and vortex-induced-vibration (VIV). A unified theoretical frame work that describes the flutter phenomenon observed in both "stiff" and "flexible" materials for flow driven energy harvester was presented in this work. We prove flutter in both types of materials is the results of the coupled effects of torsional and bending modes. Compared to "stiff" materials, which has a flow velocity-independent flutter frequency, flexible material presents a flutter frequency that almost linearly scales with the flow velocity...
October 14, 2016: Scientific Reports
Stephen P Brazier, Vsevolod Telezhkin, Paul J Kemp
Proteomic studies have suggested a biochemical interaction between α subunit of the large conductance, voltage- and Ca(2+)-activated potassium channel (BKCaα), and annexin A5 (ANXA5), which we verify here by coimmunoprecipitation and double labelling immunocytochemistry. The observation that annexin is flipped to the outer membrane leaflet of the plasma membrane during apoptosis, together with the knowledge that the intracellular C-terminal of BKCaα contains both Ca(2+)-binding and a putative annexin-binding motif, prompted us to investigate the functional consequences of this protein partnership to cell death...
2016: Oxidative Medicine and Cellular Longevity
Mark A Corbett, Susannah T Bellows, Melody Li, Renée Carroll, Silvana Micallef, Gemma L Carvill, Candace T Myers, Katherine B Howell, Snezana Maljevic, Holger Lerche, Elena V Gazina, Heather C Mefford, Melanie Bahlo, Samuel F Berkovic, Steven Petrou, Ingrid E Scheffer, Jozef Gecz
OBJECTIVE: To identify the genetic basis of a family segregating episodic ataxia, infantile seizures, and heterogeneous epilepsies and to study the phenotypic spectrum of KCNA2 mutations. METHODS: A family with 7 affected individuals over 3 generations underwent detailed phenotyping. Whole genome sequencing was performed on a mildly affected grandmother and her grandson with epileptic encephalopathy (EE). Segregating variants were filtered and prioritized based on functional annotations...
October 12, 2016: Neurology
Yibo Wang, Jiqing Guo, Laura L Perissinotti, James Lees-Miller, Guoqi Teng, Serdar Durdagi, Henry J Duff, Sergei Yu Noskov
Mutations that reduce inactivation of the voltage-gated Kv11.1 potassium channel (hERG) reduce binding for a number of blockers. State specific block of the inactivated state of hERG block may increase risks of drug-induced Torsade de pointes. In this study, molecular simulations of dofetilide binding to the previously developed and experimentally validated models of the hERG channel in open and open-inactivated states were combined with voltage-clamp experiments to unravel the mechanism(s) of state-dependent blockade...
October 12, 2016: Scientific Reports
Sean D Boothe, Jackson D Myers, Seokwon Pok, Junping Sun, Yutao Xi, Raymond M Nieto, Jie Cheng, Jeffrey G Jacot
The stiffness of myocardial tissue changes significantly at birth and during neonatal development, concurrent with significant changes in contractile and electrical maturation of cardiomyocytes. Previous studies by our group have shown that cardiomyocytes generate maximum contractile force when cultured on a substrate with a stiffness approximating native cardiac tissue. However, effects of substrate stiffness on the electrophysiology and ion currents in cardiomyocytes have not been fully characterized. In this study, neonatal rat ventricular myocytes were cultured on the surface of flat polyacrylamide hydrogels with elastic moduli ranging from 1 to 25 kPa...
October 8, 2016: Cell Biochemistry and Biophysics
T Z Lu, W Kostelecki, C L F Sun, N Dong, J L Pérez Velázquez, Z-P Feng
The spontaneous rhythmic firing of action potentials in pacemaker neurons depends on the biophysical properties of voltage-gated ion channels and background leak currents. The background leak current includes a large K(+) and a small Na(+) component. We previously reported that a Na(+) -leak current via U-type channels is required to generate spontaneous action potential firing in the identified respiratory pacemaker neuron, RPeD1, in the freshwater pond snail Lymnaea stagnalis. We further investigated the functional significance of the background Na(+) current in rhythmic spiking of RPeD1 neurons...
October 6, 2016: European Journal of Neuroscience
Jun Wei Li, Shao Ying Xiao, Xiao Xiao Xie, Hui Zhou, Chun Li Pang, Shan Shan Li, Hai Lin Zhang, Diomedes E Logothetis, Yong Zhan, Hai Long An
Kir2.1 (also known as IRK1) plays key roles in regulation of resting membrane potential and cell excitability. To achieve its physiological roles, Kir2.1 performs a series of conformational transition, named as gating. However, the structural basis of gating is still obscure. Here, we combined site-directed mutation, two-electrode voltage clamp with molecular dynamics simulations and determined that H221 regulates the gating process of Kir2.1 by involving a weak interaction network. Our data show that the H221R mutant accelerates the rundown kinetics and decelerates the reactivation kinetics of Kir2...
October 3, 2016: Proteins
Huan Wang, Hong-Fei Wang, Hao Zhang, Chen Wang, Yu-Fang Chen, Rong Ma, Ji-Zhou Xiang, Xin-Ling Du, Qiang Tang
AIM: Voltage-gated sodium channels composed of a pore-forming α subunit and auxiliary β subunits are responsible for the upstroke of the action potential in cardiac myocytes. The pore-forming subunit of the cardiac sodium channel Nav1.5, which is encoded by SCN5A, is the main ion channel that conducts the voltage-gated cardiac sodium current (INa) in cardiac cells. The current study sought to investigate the inhibitory effects of hesperetin (HSP) on human cardiac Nav1.5 channels stably expressed in human embryonic kidney 293 (HEK 293) cells and on the voltage-gated cardiac sodium current (INa) in human atrial myocytes...
October 3, 2016: Acta Pharmacologica Sinica
Leonardo Lara-Valderrábano, Luisa Rocha, Emilio J Galván
Propylparaben (PPB) is an antimicrobial preservative widely used in food, cosmetics, and pharmaceutics. Virtual screening methodologies predicted anticonvulsant activity of PPB that was confirmed in vivo. Thus, we explored the effects of PPB on the excitability of hippocampal neurons by using standard patch clamp techniques. Bath perfusion of PPB reduced the fast-inactivating sodium current (INa) amplitude, causing a hyperpolarizing shift in the inactivation curve of the INa, and markedly delayed the sodium channel recovery from the inactivation state...
September 28, 2016: Neurotoxicology
Zhi-Gang Huang, Hao-Wen Liu, Zhen-Zhen Yan, Sheng Wang, Lu-Yang Wang, Jiu-Ping Ding
Large-conductance Ca(2+)- and voltage- activated potassium (MaxiK or BK) channels are composed of a pore-forming α subunit (Slo) and four types of auxiliary β subunits or just a pore-forming α subunit. Although multiple N-linked glycosylation sites in the extracellular loop of β subunits have been identified, very little is known about how glycosylation influences the structure and function of BK channels. Using a combination of site-directed mutagenesis, western blot and patch-clamp recordings, we demonstrated that three sites in the extracellular loop of β2 subunit are N-glycosylated (N-X-T/S at N88, N96 and N119)...
October 3, 2016: Channels
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