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 effect of cadmium on the light-sensitive current of isolated rods of the tiger salamander was analysed by rapidly changing the ionic medium using the technique of Hodgkin et al. (1985). Addition of millimolar amounts of cadmium to the extracellular medium caused a rapid, but transient, decrease of the photocurrent. The effect of cadmium on the movement of divalent cations, such as Ba2+ and Ca2+, differs according to the experimental protocol: when cadmium is introduced into the bathing medium at the same time as Ca2+ or Ba2+, it blocks the entry of these ions into the rod; and when the rod is exposed to cadmium first for a few seconds the entry of Ca2+ and Ba2+ is enhanced. The effect of cadmium is best explained as a dual effect: firstly, an external effect on the channel, and secondly, by metabolic changes, which are caused by a drop of intracellular Ca2+.
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PMID:The effect of cadmium on the light-sensitive current of isolated rods of the tiger salamander. 247 89

The calcium current of bullfrog sympathetic neurons activates and deactivates rapidly (tau less than 3 ms). For brief depolarizations, the current can be fit reasonably well by a Hodgkin-Huxley-type model with a single gating particle of charge +3. With 2 mM Ca2+ as the charge carrier, half-maximal activation occurs at approximately -5 mV, near the voltage where activation and deactivation are slowest. When extracellular divalent ion concentrations are reduced, monovalent ions (e.g., Na+ and methylammonium) produce kinetically similar inward currents. Current carried by Ba2+ is blocked by Cd2+ at micromolar concentrations, and by 100 nM omega-conotoxin. Commercially available saxitoxin blocks the current, but different batches have quantitatively different potency. The dihydropyridine agonist Bay K 8644 induces a slight shift in activation kinetics to more negative voltages, with little effect on the peak current. Nifedipine at least partially reverses the effect of Bay K 8644, but has little effect on its own. Muscarinic agonists and other ligands that inhibit the M-type potassium current of frog sympathetic neurons have weak inhibitory effects on the calcium current as well. One interpretation of these results is that the N-type calcium current predominates in these cells, with a minor contribution of L-type current.
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PMID:Calcium currents in bullfrog sympathetic neurons. I. Activation kinetics and pharmacology. 247 59

Ca2+ inward currents evoked by membrane depolarization have been studied by the intracellular dialysis technique in the somatic membrane of isolated dorsal root ganglion neurones of new-born rats. In about 20% of the investigated cells a hump has been detected on the descending branch of the current-voltage curve, indicating the presence of two populations of Ca2+ channels differing in their potential-dependent characteristics. An initial less regular component of the Ca2+ current was activated at membrane potentials from -75 to -70 mV. Its amplitude reached 0.2-0.9 nA at 14.6 mM-extracellular Ca2+. The activation kinetics of this component could be approximated by the Hodgkin-Huxley equation using the square of the m variable. tau m varied in the range from 8 to 1 ms at potentials between -60 and -25 mV ('fast' Ca2+ current). The second component of the Ca2+ current was activated at membrane depolarizations to between -55 and -50 mV. It could be recorded in all cells investigated and reached a maximum value of 1-7 nA at the same extracellular Ca2+ concentration. This component decreased rapidly during cell dialysis with saline solutions. The decrease could be slowed down by cooling and accelerated by warming the extracellular solution. Intracellular introduction of 3',5'-cAMP together with ATP and Mg2+ not only prevented the decrease but often restored the maximal current amplitude to its initial level. The activation kinetics of this component could also be approximated by a square function, tau m being in the range 16-2.5 ms at membrane potentials between -20 and +3 mV ('slow' Ca2+ current). The fast Ca2+ current inactivated exponentially at sustained depolarizations in a potential-dependent manner, tau h varying from 76 to 35 ms at potentials between -50 and -30 mV. The inactivation of the slow Ca2+ current studied in double-pulse experiments was current-dependent and developed very slowly (time constant of several hundreds of milliseconds). It slowed down even more at low temperature or after substitution of Ba2+ for Ca2+ in the extracellular solution. Both currents could also be carried by Ba2+ and Sr2+, although the ion-selecting properties of the two types of channels showed quantitative differences. Specific blockers of Ca2+ channels (Co2+, Mn2+, Cd2+, Ni2+ or verapamil) exerted similar effects on them. The existence of metabolically dependent and metabolically independent Ca2+ channels in the neuronal membrane and their possible functional role are discussed.
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PMID:Two types of calcium channels in the somatic membrane of new-born rat dorsal root ganglion neurones. 258 15

Currents were generated by depolarizing pulses in voltage-clamped, dissociated neurons from the CA1 region of adult guinea pig hippocampus in solutions containing 1 microm tetrodotoxin. When the extracellular potassium concentration was 100 mM, the currents reversed at -8.1 +/- 1.6 mV (n = 5), close to the calculated potassium equilibrium potential of -7 mV. The currents were depressed by 30 mM tetraethylammonium in the extracellular solution but were unaffected by 4-aminopyridine at concentrations of 0.5 or 1 mM. It was concluded that the currents were depolarization-activated potassium currents. Instantaneous current-voltage curves were nonlinear but could be fitted by a Goldman-Hodgkin-Katz equation with PNa/PK = 0.04. Conductance-voltage curves could be described by a Boltzmann-type equation: the average maximum conductance was 65.2 +/- 15.7 nS (n = 9) and the potential at which gK was half-maximal was -4.8 +/- 3.9 mV (mean +/- 1 SEM, n = 10). The relationship between the null potential and the extracellular potassium concentration was nonlinear and could be fitted by a Goldman-Hodgkin-Katz equation with PNa/PK = 0.04. The rising phase of potassium currents and the decay of tail currents could be fitted with exponentials with single time constants that varied with membrane potential. Potassium currents inactivated to a steady level with a time constant of approximately 450 ms that did not vary with potential. The currents were depressed by substituting cobalt or cadmium for extracellular calcium but similar effects were not obtained by substituting magnesium for calcium.
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PMID:Potassium current activated by depolarization of dissociated neurons from adult guinea pig hippocampus. 284 59

1. Instantaneous current-voltage (I-V) relations were measured from tail currents with 10 mM-external calcium at 20 degrees C. The I-V relations had a lower potential dependence than predicted by the Goldman-Hodgkin-Katz constant-field equation. Previously proposed symmetric two-site three-barrier (2S3B) rate theory models were able to account for the I-V relations reasonably well. 2. Reversal of the current flow through the calcium channels was recorded using 10 mM-barium internally and 20 mM-barium externally. The channels appeared to rectify at positive potentials, a property not consistent with symmetric rate theory models. 3. Externally applied cadmium ions blocked the calcium channels through at least two sites. One high-affinity blocking site was located within the membrane electric field and had a dissociation constant of around 16 microM at O mV. Cadmium block at this site was relieved with hyperpolarization with a voltage dependence equivalent to a divalent cation moving through about 75% of the membrane electric field. 4. A low-affinity potential-independent blocking site also appeared to be present, having a dissociation constant of around 106 microM. 5. Cadmium had significant effects on the tail current kinetics at potentials close to 0 mV, presumably due to slow unblocking events. The rate at which cadmium ions left the calcium channel free to conduct was estimated to be about 3300 s-1 at +10 mV.
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PMID:Permeation of barium and cadmium through slowly inactivating calcium channels in cat sensory neurones. 285 42

Properties of the delayed outward current (IK) in ventricular myocytes of the guinea-pig were studied using the whole cell clamp method. The experiments were performed under conditions in which IK was enhanced by application of isoproterenol while the Ca2+ current was eliminated by Ca2+-removal and by the addition of Cd2+. The reversal potential (Erev) of IK, determined from the current tails, was about 10 mV less negative than the K+ equilibrium potential. This was estimated by examining the reversal potential of the inward rectifier K+ current in Ba2+-containing solution, or from the Nernst equation. The Erev--log[K+]o relationship had a slope of 49 mV per tenfold change in [K+]o. In Na+-free solution, Erev became more negative. Thus, although the major charge carriers in IK are K+ ions, Na+ ions may also contribute in part to this current. The PNa/PK ratio in IK, calculated by applying a Goldman-Hodgkin-Katz relation to the reversal potential, was 0.016. The activation of IK during depolarization showed a sigmoidal time course at the onset, while the time course of the current tails was monoexponential at voltages more negative than-50 mV, but biexponential at more positive voltages. These observations can be explained by the conductance equation of the Hodgkin-Huxley type in which the kinetic variable is raised to the second power. These and other features of IK observed in the ventricular cells are discussed in comparison to the properties of similar current systems reported in other cardiac preparations.
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PMID:An analysis of the delayed outward current in single ventricular cells of the guinea-pig. 344 99

The relationship between inward current and contraction was studied with double sucrose gap technique and measurement of contraction of the small muscular bundle in circular muscle from the fundus of guinea pig stomach. In voltage-clamped circular muscle, an inward current observed during depolarizing potential step was sensitive to Cd2+ or low external Ca2+ and had two components: a transient and a steady-state ones. Inactivation of this current was both voltage-dependent and Ca-current-dependent. Transient inward current activated phasic contraction, while the steady-state current activated tonic contraction. The voltage--dependence of the steady-state inward current was estimated with the Hodgkin--Huxley equation.
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PMID:[Calcium current and electromechanical coupling in the smooth muscle cells of the stomach]. 404 29

Voltage-clamp experiments using the three micro-electrode method were performed to study the temperature dependence of the calcium current ICa in intact twitch skeletal muscle fibres of the frog. Contraction was blocked by recording in hypertonic sucrose solutions. For depolarizations smaller than 0 mV the decay of the transient, slow, inward current, recorded in the presence of external tetraethylammonium (TEA+) and by replacing Cl- for CH3SO3-, followed a complex time course. For larger depolarizations, after the initial inward current, there was a prominent, slow, outward current which showed two phases: after reaching a peak (time to peak 1.0 sec, peak amplitude 20-50 microA/cm2 at 20 mV) it slowly declined to a steady level in about 2-3 sec at 23 degrees C. The inward current was greatly reduced or abolished by the adding of 2 mM-Cd2+ or by replacing external Ca2+ with Mg2+. The amplitude and time course of slow, outward currents were not obviously modified by replacing Ca2+ with Mg2+, having the two described phases. However, in the presence of Cd2+ the first transient phase of the outward current was not detected and only outward currents slowly increasing to a steady level were observed. Reliable ICa records were obtained by further blocking K+ outward currents by incubating the muscles in a K+-free TEA+- and Cs+-containing solution prior to experiments. Tubular space clamp was improved by recording ICa from small fibres with 20-30 microns radius. The decay phase of ICa under a maintained depolarization in incubated muscles was fitted by a single exponential. The corresponding rate constant determined between 12 and 24 degrees C strongly depended on temperature, as expected for a gating process. The values for the activation energy and the corresponding Q10 (calculated for a 10-20 degrees C transition) were respectively: 17.5 +/- 1.0 kcal/mole and 2.9 +/- 0.2 at 0 mV, and 18.0 +/- 1.5 kcal/mole and 3.0 +/- 0.3 at -20 mV. The activation phase of ICa, analysed following the m alpha h Hodgkin-Huxley kinetic model, showed a similar temperature dependence with a Q10 of 3.0 +/- 0.3. The peak amplitude of ICa and the limiting Ca2+ permeability had a lower Q10 value of about 1.6. For a given temperature the rate constant of decay was independent of ICa peak amplitude in disagreement with a current-dependent process (intratubular Ca2+ depletion or intracellular Ca2+ accumulation) for the decay of ICa. In conclusion, our results favour a gating process (inactivation) as the principal mechanism underlying the decay phase of ICa under a maintained depolarization.
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PMID:Calcium-channel gating in frog skeletal muscle membrane: effect of temperature. 630 47

1. Voltage-dependent currents of untreated (proliferating) and lipopolysaccharide (LPS)-treated rat microglial cells in culture were recorded using the whole-cell patch-clamp technique. 2. Membrane potentials showed prominent peaks at -35 mV and -70 mV. Membrane potentials of LPS-treated cells alternated between the two values. This may be due to a negative slope region of the I-V relation resulting in two zero current potentials. 3. From a holding potential of -70 mV, hyperpolarizing steps evoked an inwardly rectifying current both in proliferating and in LPS-treated cells, while depolarizing steps below -50 mV evoked an outwardly rectifying current only in LPS-treated microglia. The currents were K+ selective, as indicated by their reversal potential of approximately 0 mV in symmetric K+ concentrations (150 mM both intra- and extracellularly) and the reversal potential of the outward tail currents of approximately -90 mV at a normal extracellular K+ concentration (4.5 mM). 4. The activation of the outward current could be fitted by Hodgkin-Huxley-type n4 kinetics. The time constant of activation depended on voltage. 5. The inactivation of the inward and outward currents could be fitted by a single exponential. The time constant of the inward current inactivation was dependent on voltage, whereas the time constant of the outward current inactivation was virtually independent of voltage, except near the threshold of activation. Recovery of the outward from inactivation was slow and could be fitted by two exponentials. Responses to depolarizing steps were stable at 0.125 Hz, but greatly decreased from the first to the second pulse at 1 Hz. 6. The inactivation of the inward, but not of the outward, current disappeared in a low Na(+)-containing medium (5 mM). The inward current was selectively inhibited by extracellular Cs+ and Ba2+. The outward current was selectively inhibited by Cd2+, 4-aminopyridine and charybdotoxin. Replacement of intracellular K+ by an equimolar concentration of Cs+, and the extracellular application of tetraethylammonium and quinine inhibited both currents. 7. An increase of extracellular Ca2+ from 2 to 20 mM resulted in outwardly rectifying K+ channels activating at more positive potentials. Omission of Ca2+ from the extracellular medium had the opposite effect. When the intracellular free Ca2+ was increased from 0.01 to 1 microM, the outward current amplitudes were depressed. The Ca2+ ionophore A23187 had a similar effect. 8. LPS-treated microglial cells possess inwardly and outwardly rectifying K+ channels. The physiological and pharmacological characteristics of these two channel populations are markedly different.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Voltage-dependent potassium channels in activated rat microglia. 751 64

The activation marker CD30 is expressed on the cell surface of the malignant cells in Hodgkin's disease and a few non-Hodgkin lymphomas. We have analyzed the regulation of membrane-bound CD30 and found that the binding of a variety of anti-CD30 antibodies induced down-regulation of CD30 on cell lines. In addition, such down-modulation was also observed after treatment of the cell surface proteins with the sulfhydryl reagent iodoacetamide or after stimulation of the second messenger pathway with phorbol ester or calcium ionophore. This modulation was abolished at 4 degrees C and strongly inhibited by chelators like EDTA or 1,10-phenanthroline, whereas EGTA, a selective inhibitor of Ca(2+)-dependent proteinases and other inhibitors of serine, thiol and acid proteinases, showed no effect. The down-modulation was strengthened by Zn2+ or Cd2+, but not by other divalent cations such as Fe2+, Mn2+, Mg2+, Ca2+ or Co2+, thus indicating the involvement of a zinc metalloproteinase in CD30 modulation which can be activated by protein kinase C and by alkylation of sulfhydryl groups. Pulse-chase experiments, analysis of the CD30 glycosylation and specific measurement of the 90-kDa soluble form of CD30 (sCD30) with a sandwich radioimmunoassay revealed that CD30 down-modulation results from enhanced release of 90-kDa sCD30 by the site-specific cleavage of CD30 accomplished by a zinc metalloproteinase. This release occurs at the cell membrane without prior endocytosis.
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PMID:A zinc metalloproteinase is responsible for the release of CD30 on human tumor cell lines. 759 Dec 96


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