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Channel Types (channel + type)
Selected AbstractsAuxiliary subunit regulation of high-voltage activated calcium channels expressed in mammalian cellsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 1 2004Takahiro Yasuda Abstract The effects of auxiliary calcium channel subunits on the expression and functional properties of high-voltage activated (HVA) calcium channels have been studied extensively in the Xenopus oocyte expression system, but are less completely characterized in a mammalian cellular environment. Here, we provide the first systematic analysis of the effects of calcium channel , and ,2,, subunits on expression levels and biophysical properties of three different types (Cav1.2, Cav2.1 and Cav2.3) of HVA calcium channels expressed in tsA-201 cells. Our data show that Cav1.2 and Cav2.3 channels yield significant barium current in the absence of any auxiliary subunits. Although calcium channel , subunits were in principle capable of increasing whole cell conductance, this effect was dependent on the type of calcium channel ,1 subunit, and ,3 subunits altogether failed to enhance current amplitude irrespective of channel subtype. Moreover, the ,2,, subunit alone is capable of increasing current amplitude of each channel type examined, and at least for members of the Cav2 channel family, appears to act synergistically with , subunits. In general agreement with previous studies, channel activation and inactivation gating was regulated both by , and by ,2,, subunits. However, whereas pronounced regulation of inactivation characteristics was seen with the majority of the auxiliary subunits, effects on voltage dependence of activation were only small (< 5 mV). Overall, through a systematic approach, we have elucidated a previously underestimated role of the ,2,,1 subunit with regard to current enhancement and kinetics. Moreover, the effects of each auxiliary subunit on whole cell conductance and channel gating appear to be specifically tailored to subsets of calcium channel subtypes. [source] Instream Flow Science For Sustainable River Management,JOURNAL OF THE AMERICAN WATER RESOURCES ASSOCIATION, Issue 5 2009Geoffrey E Petts Abstract:, Concerns for water resources have inspired research developments to determine the ecological effects of water withdrawals from rivers and flow regulation below dams, and to advance tools for determining the flows required to sustain healthy riverine ecosystems. This paper reviews the advances of this environmental flows science over the past 30 years since the introduction of the Instream Flow Incremental Methodology. Its central component, Physical HABitat SIMulation, has had a global impact, internationalizing the e-flows agenda and promoting new science. A global imperative to set e-flows, including an emerging trend to set standards at the regional scale, has led to developments of hydrological and hydraulic approaches but expert judgment remains a critical element of the complex decision-making process around water allocations. It is widely accepted that river ecosystems are dependent upon the natural variability of flow (the flow regime) that is typical of each hydro-climatic region and upon the range of habitats found within each channel type within each region. But as the sophistication of physical (hydrological and hydraulic) models has advanced emerging biological evidence to support those assumptions has been limited. Empirical studies have been important to validate instream flow recommendations but they have not generated transferable relationships because of the complex nature of biological responses to hydrological change that must be evaluated over decadal time-scales. New models are needed to incorporate our evolving knowledge of climate cycles and morphological sequences of channel development but most importantly we need long-term research involving both physical scientists and biologists to develop new models of population dynamics that will advance the biological basis for 21st Century e-flow science. [source] Riparian vegetation-environment relationships: complimentarity of gradients versus patch hierarchy approachesJOURNAL OF VEGETATION SCIENCE, Issue 3 2000Alan L. van Coller Arnold & de Wet (1993) Abstract. Two prominent conceptual frameworks, environmental gradients and patch hierarchies, are used in combination to describe vegetation patterns along a riparian corridor in a semi-arid South African system. We adopt both approaches, since riparian corridors are characterized by both strong environmental gradients above, away from and along the river, as well as a mosaic of patches in the geomorphology at multiple hierarchical scales. Constrained and unconstrained ordinations were used to determine the variability in vegetation pattern accounted for by the gradient and the geomorphic patch hierarchy data sets. The gradient data set consisted of vertical, lateral and longitudinal dimensions of the macro-channel, while the patch hierarchy data set consisted of substratum type, morphological unit and channel type. Elevation up the macro-channel bank, of the gradient data set, explained the main variation in vegetation pattern, and alluded to overriding processes of flooding frequency and water availability as determinants of vegetation pattern. Along the fluvially dynamic macro-channel floor (lower elevation range), patchiness at the scale of the morphological unit best explained vegetation pattern. This relationship with morphological units suggests that the formation of well developed alluvial bars, and the degree of bedrock influence are important processes. The nested hierarchical framework used provided a good basis for identifying scale specific pattern in a relational manner. In systems characterized by strong environmental gradients as well as a patch mosaic at different spatial and temporal scales, the combined use of both perspectives to develop a fuller understanding of vegetation pattern is imperative and is encouraged. [source] Differences in sodium voltage-gated channel properties according to myosin heavy chain isoform expression in single muscle fibresTHE JOURNAL OF PHYSIOLOGY, Issue 21 2009F. Rannou The myosin heavy chain (MHC) isoform determines the characteristics and shortening velocity of muscle fibres. The functional properties of the muscle fibre are also conditioned by its membrane excitability through the electrophysiological properties of sodium voltage-gated channels. Macropatch-clamp is used to study sodium channels in fibres from peroneus longus (PL) and soleus (Sol) muscles (Wistar rats, n= 8). After patch-clamp recordings, single fibres are identified by SDS-PAGE electrophoresis according to their myosin heavy chain isoform (slow type I and the three fast types IIa, IIx, IIb). Characteristics of sodium currents are compared (Student's t test) between fibres exhibiting only one MHC isoform. Four MHC isoforms are identified in PL and only type I in Sol single fibres. In PL, maximal sodium current (Imax), maximal sodium conductance (gNa,max) and time constants of activation and inactivation (,m and ,h) increase according to the scheme I,IIa,IIx,IIb (P < 0.05). ,m values related to sodium channel type and/or function, are similar in Sol I and PL IIb fibres (P= 0.97) despite different contractile properties. The voltage dependence of activation (Va,1/2) shows a shift towards positive potentials from Sol type I to IIa, IIx and finally IIb fibres from PL (P < 0.05). These data are consistent with the earlier recruitment of slow fibres in a fast-mixed muscle like PL, while slow fibres of postural muscle such as soleus could be recruited in the same ways as IIb fibres in a fast muscle. [source] Anatomical characterisation of voltage gated sodium channels in the mammalian cochlear nerve spiral gangliaCLINICAL OTOLARYNGOLOGY, Issue 6 2006A. Prasai Introduction., There is evidence that Voltage Gated Sodium Channels (VGSC) may represent novel therapeutic targets for treatment of certain types of tinnitus and hearing loss. It is also known that the different VGSC types vary in their affinity for differing VGSC blockers. Parallels have been drawn with certain types of tinnitus, chronic pain and epilepsy (1) These conditions are thought to arise from pathological VGSC activity (2) There has also been empirical interest in the use of VGSC blockers as tinnitolytics, with the best known of these being intravenous lignocaine. Aim., The aim of this study was first begin to characterise VGSCs in the mammalian cochlear nerve spiral ganglion. Method., After sacrifice, guinea pigs were perfused with heparin and then 2% paraformaldehyde. The bony matrix of the cochleae was decalcified in buffer containing EGTA (8%). Decalcified tissues were embedded; frozen and 20-micron cryosections were made through the cochleae. Immunocytochemistry was then carried out using antibodies that selectively bind to individual sodium channel ,-subunits. Sections were then analysed and photographed using either an epifluorescence or a confocal microscope. Results and Conclusions., Sodium channel type 1.6 and 1.7 were shown to be expressed in the cochlear nerve spiral ganglion. Further work is being carried out to see if there are changes in the expression of these VGSC after ototrauma. These findings may help us to target our therapy to treat certain types of tinnitus and hearing loss. References 1 Smith P.F., Darlington C.L. (2005) Drug treatments for subjective tinnitus: serendipitous discovery versus rational drug design. Curr. Opin. Investig. Drugs.6, 712,716 2 Taylor C.P., Meldrum B.S. (1995) Na+ channels as targets for neuroprotective drugs. Trends. Pharmacol. Sci. 16, 309,315 [source] Coarse sediment transport in mountain streams in Colorado and Wyoming, USAEARTH SURFACE PROCESSES AND LANDFORMS, Issue 3 2005Sandra E. Ryan Abstract Since the early 1990s, US Forest Service researchers have made thousands of bedload measurements in steep, coarse-grained channels in Colorado and Wyoming, USA. In this paper we use data from 19 of those sites to characterize patterns and rates of coarse sediment transport for a range of channel types and sizes, including step,pool, plane-bed, pool,riffle, and near-braided channels. This effort builds upon previous work where we applied a piecewise regression model to (1) relate flow to rates of bedload transport and (2) define phases of transport in coarse-grained channels. Earlier, the model was tested using bedload data from eight sites on the Fraser Experimental Forest near Fraser, Colorado. The analysis showed good application to those data and to data from four supplementary channels to which the procedure was applied. The earlier results were, however, derived from data collected at sites that, for the most part, have quite similar geology and runoff regimes. In this paper we evaluate further the application of piecewise regression to data from channels with a wider range of geomorphic conditions. The results corroborate with those from the earlier work in that there is a relatively narrow range of discharges at which a substantial change in the nature of bedload transport occurs. The transition from primarily low rates of sand transport (phase I) to higher rates of sand and coarse gravel transport (phase II) occurs, on average, at about 80 per cent of the bankfull (1·5-year return interval) discharge. A comparison of grain sizes moved during the two phases showed that coarse gravel is rarely trapped in the samplers during phase I transport. Moreover, the movement and capture of the D16 to D25 grain size of the bed surface seems to correspond with the onset of phase II transport, particularly in systems with largely static channel surfaces. However, while there were many similarities in observed patterns of bedload transport at the 19 studied sites, each had its own ,bedload signal' in that the rate and size of materials transported largely reflected the nature of flow and sediment particular to that system. Published in 2005 by John Wiley & Sons, Ltd. [source] Cellular expression and functional characterization of four hyperpolarization-activated pacemaker channels in cardiac and neuronal tissuesFEBS JOURNAL, Issue 6 2001Sven Moosmang Hyperpolarization-activated cation currents (Ih) have been identified in cardiac pacemaker cells and a variety of central and peripheral neurons. Four members of a gene family encoding hyperpolarization-activated, cyclic nucleotide-gated cation channels (HCN1,4) have been cloned recently. Native Ih currents recorded from different cell types exhibit distinct activation kinetics. To determine if this diversity of Ih currents may be caused by differential expression of HCN channel isoforms, we investigated the cellular distribution of the transcripts of HCN1,4 in the murine sinoatrial node, retina and dorsal root ganglion (DRG) by in situ hybridization. In the sinoatrial node, the most prominently expressed HCN channel is HCN4, whereas HCN2 and HCN1 are detected there at moderate and low levels, respectively. Retinal photoreceptors express high levels of HCN1, whereas HCN2, 3 and 4 were not found in these cells. In DRG neurons, the dominant HCN transcript is HCN1, followed by HCN2. We next determined the functional properties of recombinant HCN1,4 channels expressed in HEK293 cells. All four channel types gave rise to Ih currents but displayed marked differences in their activation kinetics. Our results suggest that the heterogeneity of native Ih currents is generated, at least in part, by the tissue-specific expression of HCN channel genes. [source] Functional connexin "hemichannels": A critical appraisalGLIA, Issue 7 2006David C. Spray Abstract "Hemichannels" are defined as the halves of gap junction channels (also termed connexons) that are contributed by one cell; "hemichannels" are considered to be functional if they are open in nonjunctional membranes in the absence of pairing with partners from adjacent cells. Several recent reviews have summarized the blossoming literature regarding functional "hemichannels", in some cases encyclopedically. However, most of these previous reviews have been written with the assumption that all data reporting "hemichannel" involvement really have studied phenomena in which connexons actually form the permeability or conductance pathway. In this review, we have taken a slightly different approach. We review the concept of "hemichannels", summarize properties that might be expected of half gap junctions and evaluate the extent to which the properties of presumptive "hemichannels" match expectations. Then we consider functions attributed to hemichannels, provide an overview of other channel types that might fulfill similar roles and provide sets of criteria that might be applied to verify involvement of connexin hemichannels in cell and tissue function. One firm conclusion is reached. The study of hemichannels is technically challenging and fraught with opportunities for misinterpretation, so that future studies must apply rigorous standards for detection of hemichannel expression and function. At the same time there are reasons to expect surprises, including the possibility that some time honored techniques for studying gap junctions may prove unsuitable for detecting hemichannels. We advise hemichannel researchers to proceed with caution and an open mind. © 2006 Wiley-Liss, Inc. [source] Calcium channel subtypes differentially regulate fusion pore stability and expansionJOURNAL OF NEUROCHEMISTRY, Issue 4 2007Alvaro O. Ardiles Abstract Various studies have focused in the relative contribution of different voltage-activated Ca2+ channels (VACC) to total transmitter release. However, how Ca2+ entry through a given VACC subtype defines the pattern of individual exocytotic events remains unknown. To address this question, we have used amperometry in bovine chromaffin cells. L, N, and P/Q channels were individually or jointly blocked with furnidipine, ,-conotoxin GVIA, ,-agatoxin IVA, or ,-conotoxin MVIIC. The three channel types contributed similarly to cytosolic Ca2+ signals induced by 70 mmol/L K+. However, they exhibited different contributions to the frequency of exocytotic events and they were shown to differently regulate the final steps of the exocytosis. When compared with the other VACC subtypes, Ca2+ entry through P/Q channels effectively induced exocytosis, it decreased fusion pore stability and accelerated its expansion. Conversely, Ca2+ entry through N channels was less efficient in inducing exocytotic events, also slowing fusion pore expansion. Finally, Ca2+ entry through L channels inefficiently induced exocytosis, and the individual blockade of this channel significantly modified fusion pore dynamics. The distance between a given VACC subtype and the release sites could account for the differential effects of the distinct VACC on the fusion pore dynamics. [source] Melanotrope Cells of Xenopus laevis Express Multiple Types of High-Voltage-Activated Ca2+ ChannelsJOURNAL OF NEUROENDOCRINOLOGY, Issue 1 2005H.-Y. Zhang Abstract Pituitary melanotrope cells are neuroendocrine signal transducing cells that translate physiological stimuli into adaptive hormonal responses. In this translation process, Ca2+ channels play essential roles. We have characterised which types of Ca2+ current are present in melanotropes of the amphibian Xenopus laevis, using whole-cell, voltage-clamp, patch-clamp experiments and specific blockers of the various current types. Running an activation current,voltage relationship protocol from a holding potential (HP) of ,80 mV/or ,110 mV, shows that Xenopus melanotropes possess only high-voltage activated (HVA) Ca2+ currents. Steady-state inactivation protocols reveal that no inactivation occurs at ,80 mV, whereas 30% of the current is inactivated at ,30 mV. We determined the contribution of individual channel types to the total HVA Ca2+ current, examining the effect of each channel blocker at an HP of ,80 mV and ,30 mV. At ,80 mV, ,-conotoxin GVIA, ,-agatoxin IVA, nifedipine and SNX-482 inhibit Ca2+ currents by 21.8 ± 4.1%, 26.1 ± 3.1%, 24.2 ± 2.4% and 17.9 ± 4.7%, respectively. At ,30 mV, ,-conotoxin GVIA, nifedipine and ,-agatoxin IVA inhibit Ca2+ currents by 33.8 ± 3.0, 24.2 ± 2.6 and 16.0 ± 2.8%, respectively, demonstrating that these blockers substantially inhibit part of the Ca2+ current, independently from the HP. We have previously demonstrated that ,-conotoxin GVIA can block Ca2+ oscillations and steps. We now show that nifedipine and ,-agatoxin IVA do not affect the intracellular Ca2+ dynamics, whereas SNX-482 reduces the Ca2+ step amplitude. We conclude that Xenopus melanotrope cells express all four major types of HVA Ca2+ channel, as well as the resulting currents, but no low-voltage activated channels. The results provide the basis for future studies on the complex regulation of channel-mediated Ca2+ influxes into this neuroendocrine cell type as a function of its role in the animal's adaptation to external challenges. [source] Molecular determinants of inactivation in voltage-gated Ca2+ channelsTHE JOURNAL OF PHYSIOLOGY, Issue 2 2000Steffen Hering Evolution has created a large family of different classes of voltage-gated Ca2+ channels and a variety of additional splice variants with different inactivation properties. Inactivation controls the amount of Ca2+ entry during an action potential and is, therefore, believed to play an important role in tissue-specific Ca2+ signalling. Furthermore, mutations in a neuronal Ca2+ channel (Cav2.1) that are associated with the aetiology of neurological disorders such as familial hemiplegic migraine and ataxia cause significant changes in the process of channel inactivation. Ca2+ channels of a given subtype may inactivate by three different conformational changes: a fast and a slow voltage-dependent inactivation process and in some channel types by an additional Ca2+ -dependent inactivation mechanism. Inactivation kinetics of Ca2+ channels are determined by the intrinsic properties of their pore-forming ,1 -subunits and by interactions with other channel subunits. This review focuses on structural determinants of Ca2+ channel inactivation in different parts of Ca2+ channel ,1 -subunits, including pore-forming transmembrane segments and loops, intracellular domain linkers and the carboxyl terminus. Inactivation is also affected by the interaction of the ,1 -subunits with auxiliary ,-subunits and intracellular regulator proteins. The evidence shows that pore-forming S6 segments and conformational changes in extra- (pore loop) and intracellular linkers connected to pore-forming segments may play a principal role in the modulation of Ca2+ channel inactivation. Structural concepts of Ca2+ channel inactivation are discussed. [source] Habitat selection of freshwater-dependent cetaceans and the potential effects of declining freshwater flows and sea-level rise in waterways of the Sundarbans mangrove forest, BangladeshAQUATIC CONSERVATION: MARINE AND FRESHWATER ECOSYSTEMS, Issue 2 2009B.D. Smith Abstract 1.Generalized additive models of sighting data for cetaceans collected during two surveys of waterways in the Sundarbans mangrove forest of Bangladesh indicated that Ganges River dolphin Platanista gangetica gangetica distribution was conditionally dependent (P<0.05) on low salinity, high turbidity, and moderate depth during both low and high freshwater flow; and Irrawaddy dolphin Orcaella brevirostris distribution was conditionally dependent (P<0.05) on low salinity during high freshwater flow, high and moderate depths during low and high freshwater flow, respectively; low and high-low extremes of turbidity during low and high freshwater flow, respectively; and high temperature and increasing numbers of large,small channel confluences during low freshwater flow. 2.According to sighting data collected over a 3-year period by the captains of three nature tourism vessels, there were significant differences between the actual and expected frequencies of Ganges River dolphin sightings and individuals according to various channel types (chi-square=64.22, P<0.0001 and chi-square=134.14, P<0.0001, respectively, df=6) and of Irrawaddy dolphin sightings and individuals (chi-square=15.28, P=0.0182, and chi-square=29.42, P<0.0001, respectively, df=6), with shared preferences for wide sinuous channels with at least two small confluences or one large confluence. 3.The dependency exhibited by both species for environmental characteristics associated with abundant freshwater flow, including low salinity and the availability of confluences, make them particularly vulnerable to habitat loss due to upstream water abstraction and sea-level rise. 4.Although the results of this study may not affect plans for construction in India of large-scale, inter-basin water transfer projects that will result in further declines in freshwater flows, or decisions within the international community about CO2 emissions affecting global sea levels, they can be used to prioritize locations where protective measures could be employed to benefit the long-term conservation of both species. Copyright © 2008 John Wiley & Sons, Ltd. [source] Subtype-selective targeting of voltage-gated sodium channelsBRITISH JOURNAL OF PHARMACOLOGY, Issue 6 2009Steve England Voltage-gated sodium channels are key to the initiation and propagation of action potentials in electrically excitable cells. Molecular characterization has shown there to be nine functional members of the family, with a high degree of sequence homology between the channels. This homology translates into similar biophysical and pharmacological properties. Confidence in some of the channels as drug targets has been boosted by the discovery of human mutations in the genes encoding a number of them, which give rise to clinical conditions commensurate with the changes predicted from the altered channel biophysics. As a result, they have received much attention for their therapeutic potential. Sodium channels represent well-precedented drug targets as antidysrhythmics, anticonvulsants and local anaesthetics provide good clinical efficacy, driven through pharmacology at these channels. However, electrophysiological characterization of clinically useful compounds in recombinant expression systems shows them to be weak, with poor selectivity between channel types. This has led to the search for subtype-selective modulators, which offer the promise of treatments with improved clinical efficacy and better toleration. Despite developments in high-throughput electrophysiology platforms, this has proven very challenging. Structural biology is beginning to offer us a greater understanding of the three-dimensional structure of voltage-gated ion channels, bringing with it the opportunity to do real structure-based drug design in the future. This discipline is still in its infancy, but developments with the expression and purification of prokaryotic sodium channels offer the promise of structure-based drug design in the not too distant future. [source] The developing relationship between receptor-operated and store-operated calcium channels in smooth muscleBRITISH JOURNAL OF PHARMACOLOGY, Issue 1 2002Ian McFadzean Contraction of smooth muscle is initiated, and to a lesser extent maintained, by a rise in the concentration of free calcium in the cell cytoplasm ([Ca2+]i). This activator calcium can originate from two intimately linked sources , the extracellular space and intracellular stores, most notably the sarcoplasmic reticulum. Smooth muscle contraction activated by excitatory neurotransmitters or hormones usually involves a combination of calcium release and calcium entry. The latter occurs through a variety of calcium permeable ion channels in the sarcolemma membrane. The best-characterized calcium entry pathway utilizes voltage-operated calcium channels (VOCCs). However, also present are several types of calcium-permeable channels which are non-voltage-gated, including the so-called receptor-operated calcium channels (ROCCs), activated by agonists acting on a range of G-protein-coupled receptors, and store-operated calcium channels (SOCCs), activated by depletion of the calcium stores within the sarcoplasmic reticulum. In this article we will review the electrophysiological, functional and pharmacological properties of ROCCs and SOCCs in smooth muscle and highlight emerging evidence that suggests that the two channel types may be closely related, being formed from proteins of the Transient Receptor Potential Channel (TRPC) family. British Journal of Pharmacology (2002) 135, 1,13; doi:10.1038/sj.bjp.0704468 [source] Molecular Diversity Of Vascular Potassium Channel IsoformsCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 4 2002Victoria P Korovkina SUMMARY 1. One essential role for potassium channels in vascular smooth muscle is to buffer cell excitation and counteract vasoconstrictive influences. Several molecular mechanisms regulate potassium channel function. The interaction of these mechanisms may be one method for fine-tuning potassium channel activity in response to various physiological and pathological challenges. 2. The most prevalent K+ channels in vascular smooth muscle are large-conductance calcium- and voltage-sensitive channels (maxi-K channels) and voltage-gated channels (Kv channels). Both channel types are complex molecular structures consisting of a pore-forming , -subunit and an ancillary , -subunit. The maxi-K and Kv channel , -subunits assemble as tetramers and have S4 transmembrane domains that represent the putative voltage sensor. While most vascular smooth muscle cells identified to date contain both maxi-K and Kv channels, the expression of individual , -subunit isoforms and , -subunit association occurs in a tissue-specific manner, thereby providing functional specificity. 3. The maxi-K channel , -subunit derives its molecular diversity by alternative splicing of a single-gene transcript to yield multiple isoforms that differ in their sensitivity to intracellular Ca2+ and voltage, cell surface expression and post- translational modification. The ability of this channel to assemble as a homo- or heterotetramer allows for fine-tuning control to intracellular regulators. Another level of diversity for this channel is in its association with accessory , -subunits. Multiple , -subunits have been identified that can arise either from separate genes or alternative splicing of a , -subunit gene. The maxi-K channel , -subunits modulate the channel's Ca2+ and voltage sensitivity and kinetic and pharmacological properties. 4. The Kv channel , -subunit derives its diverse nature by the expression of several genes. Similar to the maxi-K channel, this channel has been shown to assemble as a homo- and heterotetramer, which can significantly change the Kv current phenotype in a given cell type. Association with a number of the ancillary , -subunits affects Kv channel function in several ways. Beta-subunits can induce inactivating properties and act as chaperones, thereby regulating channel cell-surface expression and current kinetics. [source] | ||||||||||||||||