Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019829 (Hodgkin's disease)
 30,247 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The conductance and selectivity of the Ca-activated K channel in cultured rat muscle was studied. Shifts in the reversal potential of single channel currents when various cations were substituted for Ki+ were used with the Goldman-Hodgkin-Katz equation to calculate relative permeabilities. The selectivity was Tl+ greater than K+ greater than Rb+ greater than NH4+, with permeability ratios of 1.2, 1.0, 0.67, and 0.11. Na+, Li+, and Cs+ were not measurably permeant, with permeabilities less than 0.05 that of K+. Currents with the various ions were typically less than expected on the basis of the permeability ratios, which suggests that the movement of an ion through the channel was not independent of the other ions present. For a fixed activity of Ko+ (77 mM), plots of single channel conductance vs. activity of Ki+ were described by a two-barrier model with a single saturable site. This observation, plus the finding that the permeability ratios of Rb+ and NH+4 to K+ did not change with ion concentration, is consistent with a channel that can contain a maximum of one ion at any time. The empirically determined dissociation constant for the single saturable site was 100 mM, and the maximum calculated conductance for symmetrical solutions of K+ was 640 pS. TEAi+ (tetraethylammonium ion) reduced single channel current amplitude in a voltage-dependent manner. This effect was accounted for by assuming voltage-dependent block by TEA+ (apparent dissociation constant of 60 mM at 0 mV) at a site located 26% of the distance across the membrane potential, starting at the inner side. TEAo+ was much more effective in reducing single channel currents, with an apparent dissociation constant of approximately 0.3 mM.
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PMID:Ion conductance and selectivity of single calcium-activated potassium channels in cultured rat muscle. 608 5

The relative permeability of endplate channels to many organic cations was determined by reversal-potential criteria. Endplate currents induced by iontophoretic "puffs" of acetylcholine were studied by a Vaseline gap, voltage clamp method in cut muscle fibers. Reversal potential changes were measured as the NaCl of the bathing medium was replaced by salts of organic cations, and permeability ratios relative to Na+ ions were calculated from the Goldman-Hodgkin-Katz equation. 40 small monovalent organic cations had permeability ratios larger than 0.1. The most permeant including NH4+, hydroxylamine, hydrazine, methylamine, guanidine, and several relatives of guanidine had permeability ratios in the range 1.3--2.0. However, even cations such as imidazole, choline, tris(hydroxymethyl)aminomethane, triethylamine, and glycine methylester were appreciably permeant with permeability ratios of 0.13--0.95. Four compounds with two charged nitrogen groups were also permeant. Molecular models of the permeant ions suggest that the smallest cross-section of the open pore must be at least as large as a square, 6.5 A x 6.5 A. Specific chemical factors seem to be less important than access or friction in determining the ionic selectivity of the endplate channel.
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PMID:The permeability of the endplate channel to organic cations in frog muscle. 624 22

1. Na channel reversal potentials were studied in perfused voltage clamped squid giant axons. The concentration dependence of ion selectivity was determined with both external and internal changes in Na and ammonium concentrations. 2. A tenfold change in the internal ammonium activity results in a 42 mV shift in the reversal potential, rather than the 56 mV shift expected from the Goldman, Hodgkin, Katz equation for a constant PNa/PNH4 ratio. However, changing [Na]o tenfold at constant internal [NH4] gives approximately the expected 56 mV shift. Therefore, the apparent channel selectivity depends upon the internal ammonium concentration but not the external Na concentration. 3. With ammonium outside and Na inside, the calculated permeability ratio is nearly constant, regardless of the permeant ion concentration. 4. Internal Cs ions can alter the Na/K permeability ratio. 5. The results are considered in terms of a three-barrier, two-site ionic permeation model.
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PMID:Sodium channel permeation in squid axons. I: Reversal potential experiments. 625 34

Delayed potassium channels were studied in internally perfused neurone somata from land snails. Relaxation and fluctuation analysis of this class of ion channels revealed Hodgkin-Huxley type K channels with an average single channel conductance (gamma K) of 2.40 +/- 0.15 pS. The conductance of open channels is independent of voltage and virtually all K channels seem to be open at maximum K conductance (gk) of the membrane. Voltage dependent time constants of activation of gK, calculated from K current relaxation and from cut-off frequencies of power spectra, are very similar indicating dominant first-order kinetics. Ion selectivity of K channels was studied by ion substitution in the external medium and exhibited the following sequence: Tl+ greater than K+ greater than Rb+ greater Cs+ greater than NH4+ greater Li+ greater than Na+. The sequence of the alkali cations does not conform to any of the sequences predicted by Eisenman's theory. However, the data are well accommodated by a new theory assuming a single rate-limiting barrier that governs ion movement through the channel.
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PMID:Ion conductance and ion selectivity of potassium channels in snail neurones. 625 61

The transepithelial fluxes, conductances and permeabilities of Li+, Na+, K+, Cs+, NH4+ and H3CNH3+ were studied under ionic concentrations ranging from 12 to 250 mM in Bufo arenarum gallbladders. When these measurements are carefully corrected in order to get only the component due to the paracellular cation channels, the following results are obtained: (1) The permeability ratios (cationic/anionic) are a decreasing function of salt concentration. (2) The partial conductances through paracellular cationic channels show nonlinear saturable concentration kinetics. (3) Moreover, partial conductance kinetics of K+, Cs+ and NH4+ present a maximum followed, at higher concentrations, by a negative-slope region. (4) The selectivity sequences obtained from biionic potentials do not agree with those obtained from partial conductance measurements. (5) The unidirectional 22Na tracer flux (serosal to mucosal) is inhibited by 63% when the K+ symmetrical concentration in the bathing solutions is raised from 25 to 200 mM. (6) When the unidirectional 42K fluxes (serosal to mucosal) at 200 mM KCl Na-free solutions are compared with K+ partial conductance by means of the Hodgkin and Keynes (Hodgkin, A.L., Keynes, R.D. 1955, J. Physiol London 128:61-88) expression, the n' factor is 2.0. These results indicate that cations do not follow the independence principle and behave as in single-file diffusion multi-ion pores when crossing the paracellular cation channels of Bufo arenarum gallbladder epithelium.
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PMID:Single-file diffusion multi-ion mechanism of permeation in paracellular epithelial channels. 627 47

Lymphoma-associated antigen (LAA) was isolated from lymph nodes of confirmed Hodgkin's and non-Hodgkin's lymphomas by saline extraction, centrifugation and ammonium sulphate fractionation and then purified by G-200 Sephadex chromatography which revealed its mol.wt at 29 K daltons. By sucrose density-gradient centrifugation the mol.wt of LAA was 43 K daltons. Physicochemical properties of LAA were determined. In polyacrylamide gel LAA separated as a discrete protein with electrophoretic mobility of alpha-globulin at pH 8.6. The pI was 5.04 and sedimentation coefficient between 3S-4S. Xenogeneic antiserum was raised in rabbits and purified by cross adsorption and affinity chromatography. By immunochemical methods, LAA was detected in the sera and body fluids of most lymphoma patients and was absent from normal individuals and patients with other types of cancer. A radioimmunoassay procedure was developed and preliminary studies revealed that the lymphoma sera at 1:5 and 1:10 dilution inhibited the binding of labelled LAA by antibody, whereas the sera of normals and controls exhibited no such inhibition. The sensitivity of this assay was 22 ng ml-1. The serum LAA levels were in the range of 187-1500 ng ml-1. These results were also confirmed by the indirect inhibition assay using conjugated peroxidase. Serial determination of serum LAA by RIA indicated a positive correlation with the course of disease.
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PMID:Lymphoma-associated antigen (LAA): isolation, characterization and clinical evaluation. 631 41

Ion permeation properties of the glutamate receptor channel in cultured myotubes of Drosophila embryos were studied using the inside-out configuration of the patch-clamp technique. Lowering the NaCl concentration in the bath (intracellular solution), while maintaining that of the external solution constant, caused a shift of the reversal potential in the positive direction, thus indicating a higher permeability of the channel to Na+ than to Cl- (PCl/PNa < 0.04), and suggesting that the channel is cation selective. With 145 mM Na+ on both sides of the membrane, the single-channel current-voltage relation was almost linear in the voltage range between -80 and +80 mV, the conductance showing some variability in the range between 140 and 170 pS. All monovalent alkali cations tested, as well as NH4+, permeated the channel effectively. Using the Goldman-Hodgkin-Katz equation for the reversal potential, the permeability ratios with respect to Na+ were estimated to be: 1.32 for K+, 1.18 for NH4+, 1.15 for Rb+, 1.09 for Cs+, and 0.57 for Li+. Divalent cations, i.e. Mg2+ and Ca2+, in the external solution depressed not only the inward but also the outward Na+ currents, although reversal potential measurements indicated that both ions have considerably higher permeabilities than Na+ (PMg/PNa = 2.31; PCa/PNa = 9.55). The conductance-activity relation for Na+ was described by a hyperbolic curve. The maximal conductance was about 195 pS and the half-saturating activity 45 mM. This result suggests that Na+ ions bind to sites in the channel. All data were fitted by a model based on the Eyring's reaction rate theory, in which the receptor channel is a one-ion pore with three energy barriers and two internal sites.
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PMID:Ion permeation properties of the glutamate receptor channel in cultured embryonic Drosophila myotubes. 751 61

1. The effect of extracellular K+ on membrane currents of bull frog (Rana catesbeiana) taste receptor cells (TRCs) was investigated by the patch clamp and fast perfusion techniques. Extracellular K+ (2.5-90 mM) increased a TRC resting conductance and enhanced both inward and outward whole-cell currents. 2. To isolate the inward current activated by external potassium (PA current), TRCs were dialysed with 110 mM NMGCl while extracellular NaCl was replaced with NMGCl. Under these conditions, the PA current displayed an S-shaped current-voltage (I-V) curve in the -100 to 100 mV range. Extracellular Rb+ and NH4+, but not Li+, Na+ or Cs+, evoked similar currents. 3. The PA current reversal potential (Vr) did not follow the equilibrium K+ potential under experimental conditions. Therefore, K+ ions were not the only current carriers. The influence of other ions on the PA current Vr indicated that the channels involved are permeable to K+ and H+ and much less so to Na+, Ca2+ and Mg2+. Relative permeabilities were estimated on the basis of the Goldman-Hodgkin-Katz equation as follows: PH:PK:PNa = 4000:1:0.04. 4. All I-V curves of the PA current were nearly linear at low negative potentials. The slope conductance at these voltages was used to characterize the dependence of the PA current on external K+ and H+. The slope conductance versus K+ concentration was fitted by the Hill equation. The data yielded a half-maximal concentration, K1/2 = 19 +/- 3 mM and a Hill coefficient, nH = 1.53 +/- 0.36 (means +/- S.E.M.). 5. The dependence of the mean PA current and the current variance on the K+ concentration indicated a rise in the open probability of the corresponding channels as extracellular K+ was increased. With 110 mM KCl in the bath, the single channel conductance was estimated at about 6 pS. Taken together, the data suggest that extracellular K+ may serve as a ligand to activate specific small-conductance cation channels (PA channels). The mean number of the PA channels per TRC was estimated as at least 2000. 6. Extracellular Ba2+, Cd2+, Co2+, Ni2+ and Cs+ blocked the PA current in a potential-dependent manner. The PA current was blocked by Cs+ as quickly as the blocker could be applied (approximately 15 ms). The time course of the divalent cation block was well fitted by a single exponential function. The time constants were estimated at 26.5 +/- 1.9, 41.7 +/- 3.1, 56.1 +/- 4.2 and 370 +/- 18 ms at 1 mM Cd2+, Co2+, Ni2+ and Ba2+, respectively. The blocker efficiency at negative voltages followed the sequence: Cs+ > Cd2+ > Ba2+ > Ni2+ > Co2+. 7. The data indicate that protons and divalent blockers act within the PA channel pore and that H+ and the divalent ions probably act via similar mechanisms to affect the PA current. These observations and the strong pH dependence of the PA current Vr suggest that H+ occupation of the PA channel pore leading to interruption of K+ flux is the main mechanism of the pH dependence of the PA current. 8. Extracellular K+ enhanced the sensitivity of isolated TRCs to bath solution acidification due to activation of the PA channels. With 10 mM K+ in the bath, half-maximal depolarization of the TRCs was observed at pH values of 6.4-6.8. The possible role of the PA channels in sour transduction is discussed.
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PMID:Extracellular K+ activates a K(+)- and H(+)-permeable conductance in frog taste receptor cells. 951 2

The K+ and Cl- currents activated by hypotonic cell swelling were studied in Ehrlich ascites tumour cells using the whole-cell recording mode of the patch-clamp technique. Currents were measured in the absence of added intracellular Ca2+ and with strong buffering of Ca2+. K+ current activated by cell swelling was measured as outward current at the Cl- equilibrium potential (ECl) under quasi-physiological gradients. It could be abolished by replacing extracellular Na+ with K+, thereby cancelling the driving force. Replacement with other cations suggested a selectivity sequence of K+ > Rb+ > NH4 approximately Na+ approximately Li+; Cs+ appeared to be inhibitory. The current-voltage relationship of the volume-sensitive K+ current was well fitted with the Goldman-Hodgkin-Katz current equation between -130 and +20 mV with a permeability coefficient of around 10(-6) cm s(-1) with both physiological and high-K+ extracellular solutions. The class III antiarrhythmic drug clofilium blocked the volume-sensitive K+ current in a voltage-independent manner with an IC50 of 32 microM. Clofilium was also found to be a strong inhibitor of the regulatory volume decrease response of Ehrlich cells. Cell swelling-activated K+ currents of Ehrlich cells are voltage and calcium insensitive and are resistant to a range of K+ channel inhibitors. These characteristics are similar to those of the so-called background K+ channels. Noise analysis of whole-cell current was consistent with a unitary conductance of 5.5 pS for the single channels underlying the K+ current evoked by cell swelling, measured at 0 mV under a quasi-physiological K+ gradient.
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PMID:Characterisation of a cell swelling-activated K+-selective conductance of ehrlich mouse ascites tumour cells. 1079 Jan 56

A new type of shape descriptor is proposed to describe the spatial orientation for non-covalent interactions. It is built from simple, anisotropic Gaussian contributions that are parameterised by 10 adjustable values. The descriptors have been used to fit propensity distributions derived from scatter data stored in the IsoStar database. This database holds composite pictures of possible interaction geometries between a common central group and various interacting moieties, as extracted from small-molecule crystal structures. These distributions can be related to probabilities for the occurrence of certain interaction geometries among different functional groups. A fitting procedure is described that generates the descriptors in a fully automated way. For this purpose, we apply a similarity index that is tailored to the problem, the Split Hodgkin Index. It accounts for the similarity in regions of either high or low propensity in a separate way. Although dependent on the division into these two subregions, the index is robust and performs better than the regular Hodgkin index. The reliability and coverage of the fitted descriptors was assessed using SuperStar. SuperStar usually operates on the raw IsoStar data to calculate propensity distributions, e.g., for a binding site in a protein. For our purpose we modified the code to have it operate on our descriptors instead. This resulted in a substantial reduction in calculation time (factor of five to eight) compared to the original implementation. A validation procedure was performed on a set of 130 protein-ligand complexes, using four representative interacting probes to map the properties of the various binding sites: ammonium nitrogen, alcohol oxygen, carbonyl oxygen, and methyl carbon. The predicted 'hot spots' for the binding of these probes were compared to the actual arrangement of ligand atoms in experimentally determined protein-ligand complexes. Results indicate that the version of SuperStar that applies to our descriptors is capable to predict the above-mentioned atom types in ligands correctly with success rates of 59% and 74%, respectively, for all ligand atoms (regardless of their solvent accessibility), and a subset of solvent-inaccessible ones. If not only exact atom-type matches are counted, but also those that identify ligand atoms of similar physicochemical properties, the prediction rates rise to 75% and 89%. These rates are close to those obtained by the original SuperStar method (being 67% and 82%, respectively, for the prediction of exact matching atom types, and 81% and 91% in the case of predicting similar atom types).
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PMID:Simple knowledge-based descriptors to predict protein-ligand interactions. methodology and validation. 1113 70


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