SEARCH · PubMed Health

Results for “coupled patch model”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 109 records · Page 6Linked to original sources

PubMed2006

Base of pore loop is important for rectification, activation, permeation, and block of Kir3.1/Kir3.4.

The Kir3.1/Kir3.4 channel is an inward rectifier, agonist-activated K(+) channel. The location of the binding site within the channel pore that coordinates polyamines (and is thus responsible for inward rectification) and the location of the gate that opens the channel in response to agonist activation is unclear. In this study, we show, not surprisingly, that mutation of residues at the base of the selectivity filter in the pore loop and second transmembrane domain weakens Cs(+) block and decreases selectivity (as measured by Rb(+) and spermine permeation). However, unexpectedly, the mutations also weaken inward rectification and abolish agonist activation of the channel. In the wild-type channel and 34 mutant channels, there are significant (p < 0.05) correlations among the K(D) for Cs(+) block, Rb(+) and spermine permeation, inward rectification, and agonist activation. The significance of these findings is discussed. One possible conclusion is that the selectivity filter is responsible for inward rectification and agonist activation as well as permeation and block.

Amino Acid Sequence↗

PubMed1993

Does migration stabilize local population dynamics? Analysis of a discrete metapopulation model.

A discrete model for a metapopulation consisting of two local populations connected by migration is described and analyzed. It is assumed that the local populations grow according to the logistic law, that both populations have the same emigration rate, and that migrants choose their new habitat patch at random. Mathematically this leads to a coupled system of two logistic equations. A complete characterization of fixed point and two-periodic orbits is given, and a bifurcation analysis is performed. The region in the parameter plane where the diagonal is a global attractor is determined. In the symmetric case, where both populations have the same growth rate, the analysis is rigorous with complete proofs. In the nonsymmetric case, where the populations grow at different rates, the results are obtained numerically. The results are interpreted biologically. Particular attention is given to the sense in which migration has a stabilizing and synchronizing effect on local dynamics.

Animals↗

PubMed1997

Functional coupling in bovine ciliary epithelial cells is modulated by carbachol.

The functional coupling of the ciliary epithelium was studied in isolated pairs (couplets) of pigmented ciliary epithelial (PCE) and nonpigmented ciliary epithelial (NPCE) cells using the whole cell patch clamp and the fluorescent dye lucifer yellow. One cell of the pair (usually the NPCE cell of a NPCE-PCE cell couplet) was accessed with a 2-5 M omega electrode, containing 1-2 mM lucifer yellow, in the whole cell configuration of the patch clamp. After voltage-clamp experiments were completed, cells were viewed under a fluorescent microscope to confirm that the cells were coupled. The electrical coupling of the cells was also studied by calculating the capacitance (using the time-domain technique), assuming a "supercell" model for coupled cells. The mean capacitance of coupled pairs was 79.8 +/- 4.3 (SE) pF (n = 47) compared with single cell capacitances of 36.8 +/- 3.4 pF (n = 10) for PCE cells and 38.1 +/- 3.1 pF (n = 15) for NPCE cells. Octanol, carbachol (CCh), and raised extracellular Ca2+ concentration ([Ca2+]o) all caused uncoupling in pairs (couplets) of coupled NPCE and PCE cells. At room temperature (22-24 degrees C), the capacitance of the couplets decreased from 70.5 +/- 8.0 to 48.0 +/- 5.2 pF (n = 5) when exposed to octanol (1 mM), from 73.8 +/- 9.2 to 43.2 +/- 9.5 pF (n = 4) when exposed to CCh (100 microM), and from 80.5 +/- 6.7 to 49.9 +/- 7.8 pF (n = 4) when exposed to 10 mM [Ca2+]o. The response to CCh was dose dependent; at higher temperatures of 34-37 degrees C, 10 microM CCh caused a 38% reduction in capacitance, from 53.7 +/- 9.7 to 33.5 +/- 3.3 pF (n = 7) with a half-time of 249 s, and 100 microM CCh caused a 49% reduction in capacitance, from 51.3 +/- 5.6 to 26.0 +/- 2.4 pF (n = 7) with a half-time of 124 s. After pairs uncoupled and the uncoupling agent was washed out, the cell pairs often exhibited an increase in capacitance that we interpreted as "recoupling" or a reopening of the gap junctional communication pathway; the half-time for this process was 729 s after uncoupling with 100 microM CCh and 211 s after uncoupling with 10 microM CCh. This interpretation was confirmed optically by the spread of lucifer yellow into both cells of an uncoupled pair with a time course corresponding to the increase in electrical coupling. The controllable coupling of ciliary epithelial cells extends the idea of a functional syncytium involved in active transport. PCE cells take up solute and water from the blood, which then cross to NPCE cells via gap junctions and from there are secreted into the posterior chamber of the eye. Modulation of the coupling between NPCE and PCE cells may provide a mechanism to control secretion.

Animals↗

PubMedDate not supplied

Spatiotemporal dynamics of epidemics: synchrony in metapopulation models.

Multi-patch models - also known as metapopulation models - provide a simple framework within which the role of spatial processes in disease transmission can be examined. An n-patch model which distinguishes between k different classes of individuals is considered. The linear stability of spatially homogeneous solutions of such models is studied using an extension of an analysis technique previously described for a population setting in which individuals migrate between patches according to a simple linear term. The technique considerably simplifies the analysis as it decouples the nk dimensional linearized system into n distinct k-dimensional systems. An important feature of the spatial epidemiological model is that the spatial coupling may involve non-linear terms. As an example of the use of this technique, the dynamical behavior in the vicinity of the endemic equilibrium of a symmetric SIR model is decomposed into spatial modes. For parameter values appropriate for childhood diseases, expressions for the eigenvalues corresponding to in-phase and out-of-phase modes are obtained, and it is shown that the dominant mode of the system is an in-phase mode. Furthermore, the out-of-phase modes are shown to decay much more rapidly than the in-phase mode for a broad range of coupling strengths.

Communicable Diseases↗

PubMed2000

Cost of cone coupling to trichromacy in primate fovea.

Cone synaptic terminals couple electrically to their neighbors. This reduces the amplitude of temporally uncorrelated voltage differences between neighbors. For an achromatic stimulus coarser than the cone mosaic, the uncorrelated voltage difference between neighbors represents mostly noise; so noise is reduced more than the signal. Here coupling improves signal-to-noise ratio and enhances contrast sensitivity. But for a chromatic stimulus the uncorrelated voltage difference between neighbors of different spectral type represents mostly signal; so signal would be reduced more than the noise. This cost of cone coupling to encoding chromatic signals was evaluated using a compartmental model of the foveal cone array. When cones sensitive to middle (M) and long (L) wavelengths alternated regularly, and the conductance between a cone and all of its immediate neighbors was 1,000 pS (approximately 2 connexons/cone pair), coupling reduced the difference between the L and M action spectra by nearly fivefold, from about 38% to 8%. However, L and M cones distribute randomly in the mosaic, forming small patches of like type, and within a patch the responses to a chromatic stimulus are correlated. In such a mosaic, coupling still reduced the difference between the L and M action spectra, but only by 2.4-fold, to about 18%. This result is independent of the L/M ratio. Thus "patchiness" of the L/M mosaic allows cone coupling to improve achromatic contrast sensitivity while minimizing the cost to chromatic sensitivity.

Animals↗

PubMed1998

Ion permeation through a G-protein activated (GIRK1/GIRK5) inwardly rectifying potassium channel.

In order to further investigate a G-protein activated inwardly rectifying potassium channel subunit, GIRK1 was expressed in Xenopus oocytes (where it coassembles with the endogenous GIRK5). The mechanism underlying ion permeation and rectification were measured in isolated inside-out patches. Single channel current amplitudes under symmetrical K+ concentrations at different holding potentials were evaluated. Inward-rectification of K+-currents through open GIRK1/GIRK5 channels was removed by washing out polyamines and Mg2+ ions. We developed a simple 'two-sites-three-barrier' (2S3B) Eyring rate theory model of K+ ion permeation for GIRK1/GIRK5 channels. The resulting optimized parameter-set will be used as a working model for subsequent investigation regarding K+ permeation process through the GIRK1/GIRK5 channel.

Animals↗

PubMed2002

Ion channels: does each subunit do something on its own?

The advent of the patch-clamp technique 25 years ago revolutionized the study of ion channels. This method also made it possible to measure the kinetic behavior of single protein molecules. The low-noise recordings of ionic currents through single channels, coupled with other cutting-edge technologies, have revealed a rich complexity of functional states that are not readily explained by simple allosteric protein models such as the popular concerted model and the sequential model. Although these models can each account for elements of ion channel function, we propose that variations or extensions of the lesser-known general allosteric model provide a more promising framework for explaining the intricate behaviors of ion channels.

Animals↗

PubMed2006

Larger cell size in rabbits with heart failure increases myocardial conduction velocity and QRS duration.

BACKGROUND: Patients with heart failure (HF) have an increased QRS duration, usually attributed to decreased conduction velocity (CV) due to ionic remodeling but which may alternatively result from increased heart size or cellular uncoupling. We investigated the relationship between QRS width, heart size, intercellular coupling, and CV in a rabbit model of moderate HF and in computer simulations. METHODS AND RESULTS: HF was induced by pressure-volume overload. Heart weight (21.1+/-0.5 versus 10.2+/-0.4 g, mean+/-SEM; P<0.01) and QRS duration (58+/-1 versus 50+/-1 ms; P<0.01) were increased in HF versus control. Longitudinal CV (thetaL; 79+/-2 versus 67+/-4 cm/s; P<0.01) and transversal subepicardial CV (thetaT; 43+/-2 versus 37+/-2 cm/s; P<0.05) were higher in HF than in controls. Transmural CV (thetaTM) was unchanged (25+/-2 versus 24+/-1 cm/s; P=NS). Patch-clamp experiments demonstrated that sodium current was unchanged in HF versus control. Immunohistochemical experiments revealed that connexin43 content was reduced in midmyocardium but unchanged in subepicardium. Myocyte dimensions were increased in HF by approximately 30%. Simulated strands of mammalian ventricular cells (Luo-Rudy dynamic model) revealed increased thetaL and thetaT with increased myocyte size; however, increased CV could not compensate for increased strand size of longitudinally coupled cells, and consequently, total activation time was longer. CONCLUSIONS: Increased myocyte size combined with the observed expression pattern of connexin43 yields increased thetaL and thetaT and unchanged thetaTM in our nonischemic model of HF. A hypertrophied left ventricle together with insufficiently increased thetaL and unaltered thetaTM results in a prolonged QRS duration.

Animals↗

PubMed2000

Rhythmic coupling among cells in the suprachiasmatic nucleus.

In mammals, the part of the nervous system responsible for most circadian behavior can be localized to a pair of structures in the hypothalamus known as the suprachiasmatic nucleus (SCN). Previous studies suggest that the basic mechanism responsible for the generation of these rhythms is intrinsic to individual cells. There is also evidence that the cells within the SCN are coupled to one another and that this coupling is important for the normal functioning of the circadian system. One mechanism that mediates coordinated electrical activity is direct electrical connections between cells formed by gap junctions. In the present study, we used a brain slice preparation to show that developing SCN cells are dye coupled. Dye coupling was observed in both the ventrolateral and dorsomedial subdivisions of the SCN and was blocked by application of a gap junction inhibitor, halothane. Dye coupling in the SCN appears to be regulated by activity-dependent mechanisms as both tetrodotoxin and the GABA(A) agonist muscimol inhibited the extent of coupling. Furthermore, acute hyperpolarization of the membrane potential of the original biocytin-filled neuron decreased the extent of coupling. SCN cells were extensively dye coupled during the day when the cells exhibit synchronous neural activity but were minimally dye coupled during the night when the cells are electrically silent. Immunocytochemical analysis provides evidence that a gap-junction-forming protein, connexin32, is expressed in the SCN of postnatal animals. Together the results are consistent with a model in which gap junctions provide a means to couple SCN neurons on a circadian basis.

Animals↗

PubMed2004

Climate and competition: the effect of moving range boundaries on habitat invasibility.

Predictions for climate change include movement of temperature isoclines up to 1000 m/year, and this is supported by recent empirical studies. This paper considers effects of a rapidly changing environment on competitive outcomes between species. The model is formulated as a system of nonlinear partial differential equations in a moving domain. Terms in the equations describe competition interactions and random movement by individuals. Here the critical patch size and travelling wave speed for each species, calculated in the absence of competition and in a stationary habitat, play a role in determining the outcome of the process with competition and in a moving habitat. We demonstrate how habitat movement, coupled with edge effects, can open up a new niche for invaders that would be otherwise excluded.

Animals↗

PubMed2005

Ligand modulation of lateral segregation of a G-protein-coupled receptor into lipid microdomains in sphingomyelin/phosphatidylcholine solid-supported bilayers.

A growing body of evidence supports the idea that the plasma membrane bilayer is characterized by a laterally inhomogeneous mixture of lipids, having an organized structure in which lipid molecules segregate into small domains or patches. Such microdomains are characterized by high contents of sphingolipids that form thicker liquid-ordered regions that are resistant to extraction with nonionic detergents. The existence of lipid lateral segregation has been demonstrated in both model and biological membranes, although its role in protein sorting and membrane function still remains unclear. In these studies, plasmon-waveguide resonance (PWR) spectroscopy was employed to investigate the properties of microdomains in a model system consisting of a solid-supported lipid bilayer composed of a 1:1 mixture of palmitoyloleoylphosphatidylcholine (POPC) and brain sphingomyelin (SM), and their influence on the partitioning and functioning of the human delta opioid receptor (hDOR), a G-protein coupled receptor (GPCR). Resonance signals corresponding to two microdomains (POPC-rich and SM-rich) were observed in such bilayers, and the sorting of the receptor into each domain was highly dependent on the type of ligand that was bound. When no ligand was bound, the receptor was incorporated preferentially into the POPC-rich domain; when an agonist or antagonist was bound, the receptor was incorporated preferentially into the SM-rich component, although with a 2-fold greater propensity for this microdomain in the case of the agonist. Binding of G-protein to the agonist-bound receptor in the SM-rich domain occurred with a 30-fold higher affinity than binding to the receptor in the PC-rich domain. The binding of the agonist to an unliganded receptor in the bilayer produced receptor trafficking from the PC-rich to the SM-rich component. Since the SM-rich domain is thicker than the PC-rich domain, and previous studies with the hDOR have shown that the receptor is elongated upon agonist activation, we propose that hydrophobic matching between the receptor and the lipid is a driving force for receptor trafficking to the SM-rich component.

Enkephalin, D-Penicillamine (2,5)-↗

PubMed1997

Activation-dependent subconductance levels in the drk1 K channel suggest a subunit basis for ion permeation and gating.

Ion permeation and channel opening are two fundamental properties of ion channels, the molecular bases of which are poorly understood. Channels can exist in two permeability states, open and closed. The relative amount of time a channel spends in the open conformation depends on the state of activation. In voltage-gated ion channels, activation involves movement of a charged voltage sensor, which is required for channel opening. Single-channel recordings of drk1 K channels expressed in Xenopus oocytes suggested that intermediate current levels (sublevels) may be associated with transitions between the closed and open states. Because K channels are formed by four identical subunits, each contributing to the lining of the pore, it was hypothesized that these sublevels resulted from heteromeric pore conformations. A formal model based on this hypothesis predicted that sublevels should be more frequently observed in partially activated channels, in which some but not all subunits have undergone voltage-dependent conformational changes required for channel opening. Experiments using the drk1 K channel, as well as drk1 channels with mutations in the pore and in the voltage sensor, showed that the probability of visiting a sublevel correlated with voltage- and time-dependent changes in activation. A subunit basis is proposed for channel opening and permeation in which these processes are coupled.

Animals↗

PubMed1999

Inhomogeneous Reionization and the Polarization of the Cosmic Microwave Background.

In a universe with inhomogeneous reionization, the ionized patches create a second-order signal in the cosmic microwave background polarization anisotropy. This signal originates in the coupling of the free-electron fluctuation to the quadruple moment of the temperature anisotropy. We examine the contribution from a simple inhomogeneous reionization model and find that the signal from such a process is below the detectable limits of the Planck Surveyor mission. However, the signal is above the fundamental uncertainty limit from cosmic variance, so that a future detection with a high-accuracy experiment on subarcminute scales is possible.

Journal Article↗

PubMed2003

Olfactory signal transduction in the mouse septal organ.

The septal organ, a distinct chemosensory organ observed in the mammalian nose, is essentially a small island of olfactory neuroepithelium located bilaterally at the ventral base of the nasal septum. Virtually nothing is known about its physiological properties and function. To understand the nature of the sensory neurons in this area, we studied the mechanisms underlying olfactory signal transduction in these neurons. The majority of the sensory neurons in the septal organ express olfactory-specific G-protein and adenylyl cyclase type III, suggesting that the cAMP signaling pathway plays a critical role in the septal organ as in the main olfactory epithelium (MOE). This is further supported by patch-clamp recordings from individual dendritic knobs of the sensory neurons in the septal organ. Odorant responses can be mimicked by an adenylyl cyclase activator and a phosphodiesterase inhibitor, and these responses can be blocked by an adenylyl cyclase inhibitor. There is a small subset of cells in the septal organ expressing a cGMP-stimulated phosphodiesterase (phosphodiesterase 2), a marker for the guanylyl cyclase-D subtype sensory neurons identified in the MOE. The results indicate that the septal organ resembles the MOE in major olfactory signal transduction pathways, odorant response properties, and projection to the main olfactory bulb. Molecular and functional analysis of the septal organ, which constitutes approximately 1% of the olfactory epithelium, will provide new insights into the organization of the mammalian olfactory system and the unique function this enigmatic organ may serve.

Adenylyl Cyclases↗

PubMed2003

Cell coupling between ventricular myocyte pairs from connexin43-deficient murine hearts.

Mice with cardiac-restricted inactivation of the connexin43 gene (CKO mice) have moderate slowing of ventricular conduction and lethal arrhythmias. Mechanisms through which propagation is maintained in the absence of Cx43 are unknown. We evaluated gap junctional conductance in CKO ventricular pairs using dual patch clamp methods. Junctional coupling was reduced to 4+/-2 nS (side-to-side) and 11+/-2 nS (end-to-end), including 21% of cell-pairs with no detectable coupling, compared with 588+/-104 nS (side-to-side) and 558+/-92 nS (end-to-end) in control cell-pairs. Voltage dependence of control gap junctions was characteristic of Cx43. CKO conductance showed increased voltage dependence, suggesting low-level expression of other connexin isoforms. From theoretical models, this degree of CKO coupling is not expected to support levels of conduction persisting in vivo, suggesting the possibility that there are additional mechanisms for maintained propagation when gap junctional conductance is severely reduced.

Animals↗

PubMed2001

Decreased sarcoplasmic reticulum calcium content is responsible for defective excitation-contraction coupling in canine heart failure.

BACKGROUND: Altered excitation-contraction (E-C) coupling in canine pacing-induced heart failure involves decreased sarcoplasmic reticulum (SR) Ca uptake and enhanced Na/Ca exchange, which could be expected to decrease SR Ca content (Ca(SR)) and may explain the reduced intracellular Ca (Ca(i)) transient. Studies in other failure models have suggested that the intrinsic coupling between L-type Ca current (I:(Ca,L)) and SR Ca release is reduced without a change in SR Ca load. The present study investigates whether Ca(SR) and/or coupling is altered in midmyocardial myocytes from failing canine hearts (F). METHODS AND RESULTS: Myocytes were indo-1-loaded via patch pipette (37 degrees C), and Ca(i) transients were elicited with voltage-clamp steps applied at various frequencies. I(Ca,L) density was not significantly decreased in F, but steady-state Ca(i) transients were reduced to 20% to 40% of normal myocytes (N). Ca(SR), measured by integrating Na/Ca exchange currents during caffeine-induced release, was profoundly decreased in F, to 15% to 25% of N. When Ca(SR) was normalized in F by preloading in 5 mmol/L external Ca before a test pulse at 2 mmol/L Ca, a normal-amplitude Ca(i) transient was elicited. E-C coupling gain was dependent on Ca(SR) but was affected similarly in both groups, indicating that intrinsic coupling is unaltered in F. CONCLUSIONS: A decrease in Ca(SR) is sufficient to explain the diminished Ca(i) transients in F, without a change in the effectiveness of coupling. Therefore, therapeutic approaches that increase Ca(SR) may be able to fully correct the Ca handling deficit in heart failure.

Animals↗

PubMed2006

New roles for a key glycine and its neighboring residue in potassium channel gating.

Potassium channel activation regulates cellular excitability in cells such as neurons and heart. Ion channel activity relies on a switching mechanism between two conformations, the open and closed states, known as gating. It has been suggested that potassium channels are gated via a pivoted mechanism of the pore-lining helix. Our analysis suggests that hinging occurs at the residue immediately preceding the central glycine of the inner helix. Furthermore, we show that the highly conserved central glycine is necessary to prevent constraining interactions with critical residues in its vicinity, including those located in the selectivity filter. We show that such interactions can impair channel function, and that upon their removal channel activity can be restored.

Amino Acid Sequence↗

PubMed1994

Mechanosensitive fibroblasts in the sino-atrial node region of rat heart: interaction with cardiomyocytes and possible role.

The positive chronotropic response of the heart to stretch of the right atrium is one of the major mechanisms adjusting the heart rate to variations in venous return on a beat-by-beat basis. The precise pathway of this mechano-electric feedback and its cellular basis are uncertain. In this study, a possible contribution of mechanosensitive fibroblasts, abundant in the sino-atrial node region, was investigated using a mathematical model of the electrical interaction of a mechanosensitive fibroblast and a sino-atrial pacemaker cell. Electrophysiological evidence for a bio-electrical interaction of mechanosensitive fibroblasts with surrounding cardiomyocytes has been studied in (i) the isolated spontaneously beating atrium of rat hearts, and (ii) cell cultures of the neonatal rat heart. These investigations were performed using (i) double-barrelled floating microelectrodes for intracellular potential registrations, and (ii) the double whole cell patch-clamp technique. It was shown that cardiac fibroblasts and surrounding cardiomyocytes can be either electrically well isolated from each other, or coupled both capacitively and electrotonically. The electrophysiological data obtained were incorporated into the OXSOFT HEART program. Assuming that equivalent coupling may occur between mechanosensitive fibroblasts and sino-atrial pacemaker cells, a heterologous cell pair consisting of one fibroblast and one sino-atrial node myocyte connected by ten to thirty single gap junctional channels with a conductance of 30 pS was modelled. The model of the electrotonic interaction of these cells showed that stretch of the fibroblast during atrial diastole, simulating increased atrial wall tension during atrial filling, can raise the spontaneous depolarization rate of the pacemaker cell in a stretch-dependent manner by up to 24%. These results show that cardiac mechanosensitive fibroblasts could form a cellular basis for the positive chronotropic response of the heart to stretch of the right atrium.

Animals↗