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)

A chamber filled with salt solution and separated into two compartments by a Teflon partition with a pore of 700 microns diameter was used to investigate the action of aureofuscin, a polyene antibiotics, on a planar lipid bilayer. The pore was covered with a bilayer formed by a N-decane solution of lecithin and cholesterol (20 mg/ml and 5 mg/ml). The electrical property and ionic permeability of the bilayer were studied by using voltage clamp method. Decrease of the bilayer resistance and the channel-like activity could be observed 20 min after the addition of aureofuscin (10-20 micrograms/ml) to one compartment. The existence of a transmembrane voltage and ionic gradient were not necessary for the channel-forming activity of aureofuscin. Discrete current steps were recorded at a concentration of 1.4 micrograms/ml aureofuscin, with a predominant unit conductance of 4-6 pS in a symmetric KCl, solution of 100 mmol/L. By using Goldmann-Hodgkin-Katz voltage equation the ionic selectivity of the channel formed by aureofuscin was estimated by the reversal potential measured in the asymmetrical solution system. The results showed that aureofuscin channels were more permeable to potassium ion than to chloride ion (PK/PCl approximately 5.2). These data may be used to explain the action of aureofuscin on neurotransmitter release and muscle membrane potential in addition to providing some explanation on its curing effect in clinical use.
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PMID:[Ionic channels formed in the lipid bilayer membranes by aureofuscin, a polyene antibiotics]. 171 13

The usefulness of ATP-depleted rat hepatocytes in transport studies was examined. ATP-depleted hepatocytes were prepared by incubating cell suspensions with 30 microM rotenone. In ATP-depleted hepatocytes, plasma membrane permeability was increased and mitochondrial membrane potential decreased, while both intracellular volume and pH remained normal. Furthermore, in the presence of valinomycin, the initial uptake rates of 3H-tetraphenyl phosphonium (TPP+) with varied medium concentrations of potassium were predicted according to the Goldman-Hodgkin-Katz equation, which demonstrated that a potassium diffusion potential could be produced in this system. Using the thus-characterized ATP-depleted cells, the uptake mechanism of taurocholate was investigated. In the presence of an inwardly directed Na gradient, the taurocholate uptake was markedly stimulated and bile acid was transiently accumulated at a concentration 3-times higher than at equilibrium ('overshoot') in ATP-depleted cells. No overshoot was observed in viable cells, however, which suggests that in ATP-depleted cells the Na gradient, a driving force for taurocholate uptake, decreased with time. In both viable and ATP-depleted cells, the relationship between medium concentrations of Na and the Na-dependent initial uptake rate were sigmoidal, and the Hill coefficients were close to 2. The Na-dependent initial uptake rate of taurocholate was stimulated by a valinomycin-induced inside negative potassium-diffusion potential in ATP-depleted cells, and the movement of a 'one plus' (as a net) charge was revealed by fitting the data to the Goldman-Hodgkin-Katz equation. These results support the hypothesis that sodium-coupled hepatic uptake of taurocholate occuthrough an electrogenic process with the stoichiometry of 2 Na: 1 taurocholate, although this issue is controversial. In the presence of an outwardly directed sodium gradient, efflux of taurocholate from ATP-depleted cells was not stimulated. Consequently, the physiological transport vector of taurocholate from blood to cell is not only due to the direction of the sodium gradient (blood to cell) but also to membraneous orientation of transport carriers. In conclusion, kinetic analysis using ATP-depleted hepatocytes allowed the formulation of a new approach to clarify the as yet unresolved issues concerning transport stoichiometry and the mechanism for vectorial transport of taurocholate.
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PMID:Utilization of ATP-depleted cells in the analysis of taurocholate uptake by isolated rat hepatocytes. 173 16

1. The kinetics of delayed rectifier (IK) and transient potassium (IA) currents and their modification by intracellular calcium ions in bursting X-organ neurons of the crayfish were studied with whole-cell patch-clamp technique. Activation and inactivation kinetics were analyzed according to Hodgkin and Huxley-type equations. 2. IK activates with sigmoidal time course at membrane potentials more positive than -38.4 +/- 3.5 (SD) mV (n = 5), and does not inactivate. The conductance through delayed rectifier channels (gK) is described by the equation gK = GKn2. 3. IA activates at membrane potentials close to the resting potential (-52.2 +/- 4.3 mV, n = 5) and, after a peak, inactivates completely. The conductance through A-channels (gA) can be described by the product of independent activation and inactivation parameters: gA = GAa4b. Both activation and inactivation processes are voltage and time dependent. 4. Steady-state activation of IK and IA as well as inactivation of IA can be described by Boltzmann distributions for single particles with valencies of 2.55 +/- 0.01 (n = 5), 1.60 +/- 0.25 (n = 5), and 3.87 +/- 0.39 (n = 3), respectively. 5. Increasing [Ca2+]i, we observed the following: 1) a considerable inactivation of IK during test pulses, 2) an increase of maximal conductance for IA, 3) a reduction of the valency of IA inactivation gating particle (from 3.87 to 2.27), 4) a reduction of the inactivation time constants of IA, and 5) a shift of the inactivation steady-state curve to more positive membrane potentials.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Potassium current kinetics in bursting secretory neurons: effects of intracellular calcium. 176 87

A description of the activation phase of the land snail Zachrysia guanensis delayed potassium current (IK) is presented. It was found that IK activation kinetics may be congruent with the Hodgkin-Huxley scheme if one assumes that the proportion of n particles at the beginning of the pulse is not zero. In this case IK activation may be treated as carried by a homogeneous channel population, which may be relevant in view of the reported heterogeneity of the inactivation phase of this current.
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PMID:Kinetic description of the activation of the delayed potassium current of the land snail Zachrysia guanensis in terms of the Hodgkin-Huxley formalism. 177 38

1. The fully activated current-voltage relation (I-V) of the delayed rectifier potassium ion channel in squid giant axons has a non-linear dependence upon the driving force, V-EK, as I have previously demonstrated, where V is membrane potential and EK is the equilibrium potential for potassium ions. 2. The non-linearity of the I-V relation and its dependence upon external potassium ion concentration are both well described, phenomenologically, by the Goldman-Hodgkin-Katz (GHK) flux equation, as I have also previously demonstrated. As illustrated below, this result can be modelled using the Eyring rate theory of single-file diffusion of ions through a channel in the low-occupancy limit of the theory. 3. The GHK equation analysis and the low-occupancy limit of the Eyring rate theory are both consistent with the independence principle for movement of ions through the channel, which is at odds with tracer flux ratio results from the delayed rectifier, published elsewhere. Those results suggest that the channel is multiply occupied by two, or perhaps three, ions. 4. The resolution of this paradox is provided by a triple-binding site, multiple-occupancy model in which only one vacancy, at most, is allowed in the channel. This model predicts current-voltage relations which are consistent with the data (and with the phenomenological prediction of the GHK flux equation). The model is also consistent, approximately, with the tracer flux ratio results.
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PMID:A paradox concerning ion permeation of the delayed rectifier potassium ion channel in squid giant axons. 182 60

The outward current was analysed in the rapidly adapting stretch receptor neuron of the crayfish Pacifastacus leniusculus with a two-micropipette potential clamp technique and K(+)-selective microelectrodes in an attempt to establish if the properties of this current could explain the difference in adaptive behaviour compared to the slowly adapting receptor. A fast activating outward current carried by K+ was revealed. The time constant of activation(tau n) was dependent on potential and had a mean value of 0.5 ms at potential steps to 0 mV. Activation followed a second-order process according to the Hodgkin-Huxley model. The potential dependence of activation (n infinity) followed by a sigmoid curve n infinity = 1/(1 + exp/[(E - En)/a]) with a half maximal activation potential En = -44 mV and a = -13 mV. When long pulses were applied the outward potassium current decreased with two time constants, one that was potential independent (0.2 s) and one that was potential dependent (2-8 s). The latter could be explained by accumulation of K+ in the extracellular space of the neuron. The potential dependence of inactivation followed a sigmoid function infinity = 1/(1 + exp[(E - Ek)/+a]) with Ek = -36 mV and a = 13 mV. The inactivation properties are different from those of the classical fast transient (IA) current. The transport system for the outward potassium current during depolarizing potential steps in the rapidly adapting stretch receptor is similar to the current found in the slowly adapting receptor neuron. However, the activation is faster and seems to occur at potentials more negative than in the slowly adapting receptor. These differences can contribute to but not entirely explain the difference in adaptive behaviour between the slowly and rapidly adapting receptor.
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PMID:Potential-dependent potassium currents in the rapidly adapting stretch receptor neuron of the crayfish. 187 67

A computer program based on the Gauss-Newton method was developed for the Hodgkin-Huxley estimation of kinetic parameters of membrane currents recorded in voltage-clamp experiments. Fast potassium current of land snail neurons was estimated, and found to be in agreement with literature reports.
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PMID:A computer program for the estimation of kinetic parameters of membrane currents based on the Gauss-Newton method. 188 5

1. Voltage- and time-dependent outward currents were recorded from relaxed enzymatically isolated smooth muscle cells from the rabbit left descending coronary artery using a single pipette voltage clamp technique. The calcium-activated potassium current was blocked by inclusion of EGTA in the pipette solution and CdCl2 in the extracellular bath. 2. Outward currents were elicited with depolarizing voltage steps to potentials positive to -20 mV. Long (5 s) voltage steps revealed slow inactivation of the current with a time constant of nearly 3 s at +60 mV. Potassium was identified as the predominant charge carrier by reversal potential measurements in potassium substitution experiments. 3. The results of kinetic analyses compared favourably with the Hodgkin-Huxley model for a delayed rectifier with some deviations. The sigmoid current onset was best fitted by raising the activation variable (n) to the second power. Deactivation tail currents were consistently found to be comprised of two exponential components. The kinetics of activation and deactivation were strongly voltage-dependent from -80 to +60 mV. 4. Envelope of tails experiments showed that the scaled tail current amplitudes followed the kinetic behaviour of current activation. The contribution of each of the two exponential tail components was also measured in these experiments. They did not reveal kinetically separable currents, nor were they differentially altered by 4-aminopyridine (4-AP), tetraethylammonium (TEA), or elevated [K+]o. 5. The steady-state voltage-dependence curves for both activation and inactivation were well fitted by a Boltzmann distribution with V1/2 = -5.60 mV and k = -8.66 mV for n infinity act and V1/2 = -24.20 mV and k = 5.16 mV for n infinity act. Super-imposition of the two curves revealed a 'window' of voltage where channels are available for activation without completely inactivating. 6. Neither of the commonly used potassium channel blockers, TEA or 4-AP, were particularly effective blockers of IK, reducing current by only 50-70% at an extracellular concentration of 10 mM. TEA block was mildly voltage-dependent and was more effective in reducing current towards the end of a 500 ms depolarization. 4-AP, on the other hand, demonstrated considerable voltage-dependence and preferentially reduced early currents. 7. Outward currents recorded from guinea-pig and human coronary artery myocytes under the same conditions as in the rabbit cell experiments displayed similar characteristics.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:A voltage-dependent potassium current in rabbit coronary artery smooth muscle cells. 191 87

1. The patch-clamp method was applied to the study of ionic currents activated by depolarization of undifferentiated IMR-32 human neuroblastoma cells. Whole-cell sodium and potassium currents and single potassium ion channel currents from cell-attached patches were investigated. 2. Cells had a mean resting potential of -38 mV and mean input resistance of 1.6 G omega. Single action potentials were evoked under current clamp during the injection of depolarizing currents. 3. A voltage-dependent inward sodium current was observed which reversed at +44 mV. A Boltzmann fit to the activation curve gave a half-maximal activation voltage of -41.6 mV and a 'slope' of 3.9 mV. The steady-state inactivation curve had a half-maximal inactivation voltage of -81 mV and a 'slope' of 9.7 mV. 4. The time-dependent activation and inactivation of the current displayed classical Hodgkin-Huxley kinetics. Values for the time constants tau m and tau h of 0.16 and 0.63 ms were calculated for a voltage jump from -80 to -10 mV; tau m and tau h decreased as the step potential was changed from -30 to +20 mV. 5. Outward currents were activated in bathing solutions substantially free of anions and could thus be attributed to potassium ions. The tail current reversed in direction on repolarization to -60 mV when the potassium concentration in the bathing solution was increased from 6 to 30 mM. When the bathing solution contained 145 mM-potassium, and the patch pipette, 95 mM, a depolarization to -10 mV from a holding potential of -60 mV evoked an inward current. 6. Outward currents were examined by using voltage pulses which depolarized the cell to -20 mV, or more positive values, from a holding potential of -80 mV and by pulses which depolarized the cell to 0 mV, or to positive values, from a holding potential of -30 mV. A Boltzmann fit of typical activation data gave a half-maximal activation voltage of 17 mV and a 'slope' of 14 mV. 7. The time course of the rising phase of the current was described by a function of the form A(1-exp[-(t-delta t)/tau]), where delta t varied between 1 and 4 ms and tau varied between 4 and 27 ms, decreasing with increasing depolarization. There was no evidence for a fast transient component. 8. The amplitude of outward currents was reduced by extracellular calcium ions, cobalt ions, tetraethylammonium and 4-aminopyridine.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:On the sodium and potassium currents of a human neuroblastoma cell line. 202 15

The effects of some fluorinated anesthetics and convulsants on the ionic conductances of the axon membrane of the squid Loligo forbesi are described. The substances studied were the inhalation anesthetics enflurane (CF2HOCF2CClFH) and isoflurane (CF2HOCClHCF3) and the convulsants flurothyl (CF3CH2OCH2CF3) and trichlorofluormethane (CCl3F). At low concentrations (0.4-0.8 mM), none of these substances significantly affected the voltage-dependent Na and K channels of the nerve. However, at these concentrations each substance produced a depolarization of the resting potential and reduced the potassium conductance of the resting membrane. This was associated with a tendency to cause axonal hyperexcitability. The potassium conductance of the resting membrane was separated into a component arising from residual open Hodgkin-Huxley delayed rectifier K channels and another voltage-independent component (g'k). The former component was insensitive to the test substances at 0.4-0.8 mM, while g'k was inhibited by 40-80%. It is suggested that the convulsant activity of certain small fluorinated molecules, and the proconvulsant actions of certain clinical anesthetics at low concentrations, may be related to the inhibition of a resting, voltage-independent potassium conductance system in the nerve membrane.
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PMID:Effects of anesthetics and convulsants on the resting potassium conductance in squid nerve. 205 94


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