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)

Calcium current, Ica, was studied in isolated nerve cell bodies of Helix aspersa after suppression of Na+ and K+ currents. The suction pipette method described in the preceding paper was used. Ica rises to a peak value and then subsides exponentially and has a null potential of 150 mV or more and a relationship with [Ca2+]o that is hyperbolic over a small range of [Ca2+]o's. When [Ca2+]i is increased, Ica is reduced disproportionately, but the effect is not hyperbolic. Ica is blocked by extracellular Ni2+, La3+, Cd2+, and Co2+ and is greater when Ba2+ and Sr2+ carry the current. Saturation and blockage are described by a Langmuir adsorption relationship similar to that found in Balanus. Thus, the calcium conductance probably contains a site which binds the ions referred to. The site also appears to be voltage-dependent. Activation and inactivation of Ica are described by first order kinetics, and there is evidence that the processes are coupled. For example, inactivation is delayed slightly in its onset and tau inactivation depends upon the method of study. However, the currents are described equally well by either a noncoupled Hodgkin-Huxley mh scheme or a coupled reaction. Facilitation of Ica by prepulses was not observed. For times up to 50 ms, currents even at small depolarizations were accounted for by suitable adjustment of the activation and inactivation rate constants.
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PMID:The calcium current of Helix neuron. 66 Jan 60

1. Low voltage-activated (LVA) Ca2+ current in clonal (GH3) pituitary cells was studied with the use of the whole-cell recording technique. The use of internal fluoride to facilitate the rundown of high voltage-activated (HVA) Ca2+ current allowed the study of LVA current in virtual isolation. 2. In 10 mM [Ca2+]o, detectable LVA current begins to appear at about -50 mV, with half-maximal activation occurring at -33 mV. The time course of activation was best described by a Hodgkin-Huxley expression with n = 3, suggesting that at least three closed states must be traversed before channel opening. 3. Deactivation was found to vary exponentially with membrane potential between -60 and -160 mV, indicating that channel closing is rate-limited by a single, voltage-dependent transition. 4. Onset and removal of inactivation between -40 and -130 mV were best described by the sum of two exponentials. Between -80 and -130 mV, both components of removal of inactivation showed little voltage dependence, with time constants of approximately 200-300 ms and 1-2 s. At membrane potentials above -40 mV, a single component of inactivation onset was detected. This component was voltage independent between -20 and +20 mV (tau = 22 ms). Thus inactivation of LVA current is best described by multiple, voltage-in-dependent processes. 5. Significant inactivation of LVA current occurred at -65 mV without detectable macroscopic current. This suggests that inactivation is not strictly coupled to channel opening. 6. Peak LVA current increased with increasing [Ca2+]o, with saturation approximately 50 mM. The Ca(2+)-dependence of peak LVA current was reasonably well described by a single-site binding isotherm with half-maximal LVA current at approximately 7 mM. 7. LVA current in GH3 cells was largely resistant to blockade by Ni2+. The relative potency of inorganic cations in blocking GH3 LVA current was (concentrations which produced 50% block): La3+ (2.4 microM) greater than Cd2+ (188 microM) greater than Ni2+ (777 microM). 8. Several organic agents, including putative LVA blockers, HVA current blockers and various anesthetic agents, were tested for their ability to block LVA current. The concentrations that produced 50% block are as follows: nifedipine (approximately 50 microM), D600 (51 microM), diltiazem (131 microM), octanol (244 microM), pentobarbital (985 microM), methoxyflurane (1.41 mM), and amiloride (1.55 mM). Phenytoin and ethosuximide produced 36 and 10% block at 100 microM and 2.5 mM, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Kinetic and pharmacological properties of low voltage-activated Ca2+ current in rat clonal (GH3) pituitary cells. 132 46

Silver-intensification methods described in the literature for the diaminobenzidine (DAB) and diaminobenzidine-nickel (DAB/Ni) endproduct of the peroxidase reaction were compared in model systems after immunoperoxidase and in situ hybridization. First, these methods were compared in immunohistochemical model systems, using the demonstration of glial fibrillar acidic protein (GFAP) and prostate-specific antigen (PSA) in paraffin sections of human brain and prostate tissue, respectively. When DAB without Ni was used as substrate, tissue argyrophilia caused considerable background staining. Only when this tissue reactivity was quenched with, e.g., CuSO4 with H2O2 or thioglycolic acid, were the results acceptable. A considerable improvement in the signal-to-noise ratio could be obtained when nickel was included in the substrate mixture. The methods that proved to be best for demonstration of GFAP and PSA made use of acid developer solutions. Subsequently, these methods were compared with other sensitive immunostaining methods for demonstration of the gamma-delta T-cell receptor in frozen lymphoid tissue. In this model a considerable increase in the number of positive cells could be obtained using silver intensification. The different methods using DAB/Ni were also compared for use in DNA in situ hybridization (DISH). In this case two model systems were used: human papilloma virus type 11 (HPV-11) DNA in condyloma tissue (abundant target model) and Epstein-Barr virus (EBV) DNA in a mononucleosis lymph node (low target model). For demonstration of HPV-11, all methods gave more or less satisfactory results, which were best with the acid developer solutions. Moreover, for demonstration of EBV DNA, a signal could be obtained only with these developer solutions. Such a method also proved suitable in double immuno-hybrido stainings for the demonstration of EBV DNA in specific antigen-positive Reed-Sternberg cells in paraffin sections of Hodgkin lymph nodes.
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PMID:Application and comparison of silver intensification methods for the diaminobenzidine and diaminobenzidine-nickel endproduct of the peroxidation reaction in immunohistochemistry and in situ hybridization. 153 4

Two different calcium currents were revealed in the somatic membrane of Helix pomatia neurons. In addition to the main current described in literature, depolarizing the membrane from the holding potential level (-120 divided by -100 mV) an additional calcium current was observed. It was activated at depolarizations to -80 divided by -40 mV. Contrary to the main calcium current it did not deteriorate during intracellular perfusion by solutions containing fluoride. Time-dependence of this current could be described in the framework of the Hodgkin-Huxley model with time constants for activation and inactivation equal to tau m = 6-8 ms and tau h = 300-600 ms, respectively. The amplitude of this current increased with increase of extracellular Ca2+ concentration and decreased after addition of Co2+, Ni2+, Cd2+, nifedipine and verapamil. Dissociation constants of these substances with corresponding channels determined for the maximum of current-voltage relationship were 2 (Ca2+), 3 (Co2+), 0.06 (nifedipine) and 0.2 mmol/l (verapamil). Properties of the fluoride-insensitive calcium current and data obtained for other calcium channels are compared. Its possible functional role is also discussed.
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PMID:[2 calcium currents in the somatic membrane of neurons of Helix pomatia]. 241 33

1. Monovalent cation selectivity and divalent cation sensitivity of the tetrodotoxin (TTX)-resistant Na+ current in dissociated adult rat nodose ganglion neurones were investigated using the whole-cell patch-clamp technique. 2. The TTX-resistant Na+ current was isolated using ion substitution and pharmacological agents. Under these conditions, the current reversal potential shifted 52 mV per tenfold change in external [Na+]. 3. Inorganic and organic monovalent cation permeability ratios (Px/PNa) were determined from changes in reversal potential and the Goldman-Hodgkin-Katz equation. The Px/PNa values determined by the former method were HONH3+, 1.38; Li+, 1.00; H2NNH3+, 0.66; NH4+, 0.28; CH3NH3+, less than 0.13; K+, less than 0.13; Rb+, less than 0.12; Cs+, less than 0.10; (CH3)4N+, less than 0.10. The values determined by either method agreed within 10%. 4. The effects of Cd2+, Co2+, Mn2+ and Ni2+ on the TTX-resistant Na+ current were analysed from peak-conductance values. These ions shifted the activation of the current to more positive potentials and decreased the maximal conductance. At 3 mM concentrations, Cd2+, Ni2+, Co2+ and Mn2+ decreased the maximal conductance 64.6, 50.7, 25.0 and 20.3%, respectively. 5. The results indicate that: (a) the monovalent cation selectivity of the TTX-resistant Na+ current is similar to that of the TTX-sensitive Na+ current in other tissues; and (b) the TTX-resistant Na+ current is less sensitive to divalent cations than the Ca2+ current in these neurones. These observations suggest that the structure determining the monovalent cation permeability of the TTX-resistant Na+ current is similar to that of the TTX-sensitive Na+ current in other tissues, and that the channels carrying the TTX-resistant Na+ current are distinct from those responsible for the Ca2+ current.
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PMID:Tetrodotoxin-resistant sodium current of rat nodose neurones: monovalent cation selectivity and divalent cation block. 244 74

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

The concentrations of zinc, copper, nickel and chromium were determined in bone marrow and plasma of 37 patients suffering from non-Hodgkin-lymphomas (NHL). The results were compared with a control group of 10 patients with negative histopathologic results in bone marrow. The results demonstrate that all patients with low grade and high grade NHL have elevated trace element levels in bone marrow compared to the control group. In plasma there are also differences in the trace element levels of patients with NHL compared to the control group; the levels, however, are partly higher and lower than those of the control group. Altogether the plasma level differences are not as noticeable as those in the bone marrow. At the moment it is not yet possible to draw final conclusions from these results for the prognosis or therapy of NHL, but the study tends to show that intracellular measurement of trace elements is more reliable than intraplasmic measurement.
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PMID:Determination of the trace elements zinc, copper, nickel and chromium in bone marrow and plasma of patients with non-Hodgkin lymphomas. 801 52

1. Voltage-gated ionic currents were recorded from cells of an immortalized neuroepithelial cell line named V1. The cell line was produced by insertion of the temperature-sensitive tsA58 allele of the SV40 large T-antigen into embryonic day 14 mouse hypothalamic cells. V1 cells display a mixed immature neural-glial phenotype and have two phenotypes, round and flat. 2. Recordings from round V1 cells demonstrate voltage-gated Na+ and K+ currents (n = 297), while no voltage-gated currents were observed in flat V1 cells (n = 45). Voltage-gated currents were recorded from cells cultured at both permissive and restrictive temperatures. 3. Internal Cs+ and external tetraethylammonium (TEA) were used to suppress outward currents. The remaining inward current has rapid activation and inactivation time constants which decreased as the test potential increased. In different cells, the amplitude of the peak inward current varied from about 50 pA to as large as 4500 pA (in 120 mM external Na+). The reversal potential for the inward current was close to the predicted Nernst equilibrium potential for Na+. Both the magnitude and reversal potential of the inward current were dependent on the external Na+ concentration. It is therefore considered to be a Na+ current, INa. 4. INa was found to be TTX resistant. About 5% of the INa was blocked by 200 nM TTX and 20 microM TTX fully suppressed the Na+ current. The apparent Kd for TTX blockade was estimated to be 1.49 microM. 5. The activation kinetics of INa could be described by a Hodgkin-Huxley model with an m3 variable. The time constants of activation and inactivation of INa are fast, similar to those of the TTX-resistant and TTX-sensitive Na+ currents in central nervous system neurons and glial cells. 6. The divalent and trivalent cations Cd2+, Co2+, Ni2+, Zn2+ and La3+ shifted the activation of INa to more positive potentials and decreased the maximal conductance in a dose-dependent manner. The apparent Kd values for blockade of the INa by Cd2+, Co2+, Ni2+, Zn2+ and La3+ were 430, 3500, 1900, 83 and 202 microM, respectively. 7. The addition of phorbol myristate acetate, an activator of protein kinase C, consistently produced a reduction in the amplitudeof INa without affecting the time course of activation or inactivation. 8. INa in V1 cells expresses a unique combination of voltage and time kinetics and sensitivity to blockade by TTX and cations. We hypothesize that this Na+ current may be expressed transiently during development of the central nervous system at the stage of development represented by the V1 cell line.
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PMID:A novel tetrodotoxin-resistant sodium current from an immortalized neuroepithelial cell line. 874 76

1. The pharmacological and kinetic properties of two types of low-voltage-activated (LVA) Ca2+ currents were studied in thalamocortical neurones of the laterodorsal (LD) thalamic nucleus during early postnatal development. The whole-cell patch-clamp technique was used on brain slices from rats of three age groups: 12, 14 and 17 days old (postnatal day (P) 12, P14 and P17). 2. In P12 neurones, the population of LVA Ca2+ channels was homogeneous. LVA Ca2+ current elicited by depolarizing voltage steps from a holding potential more negative than -70 mV was sensitive to nifedipine (Kd = 2.6 microM). This current reached a maximum at about -55 mV and had a fast monoexponential decay with a time constant, tau h,f, of 32.3 +/- 4.0 ms. 3. The population of LVA Ca2+ channels in P14 and P17 neurones was found to be heterogeneous. A subpopulation of nifedipine-insensitive LVA Ca2+ channels was observed. The current-voltage curve of the Ca2+ current had a characteristic hump with two peaks at about -65 and -55 mV. As well as the fast component (designated IT,f), the decay of the LVA current also included a slow component (designated IT,s), with inactivation time constants (tau h,s) of 54.2 +/- 4.5 and 68.6 +/- 3.17 ms for P14 and P17 neurones, respectively. 4. The kinetics of both components could be well approximated by the m2h Hodgkin-Huxley equation. No significant difference in activation kinetics was observed. The activation time constants for the fast (tau m,f) and slow (tau m,s) components were 6.3 +/- 1.0 and 7.3 +/- 1.5 ms, respectively. 5. La3+ at a concentration of 1 microM effectively blocked the IT,f component but Ni2+ (25 microM) completely eliminated the IT,s component. 6. Steady-state inactivation curves of both components could be best fitted by a Boltzmann function with membrane potential values at half-maximal inactivation of -85.5 and -98.1 mV for the fast and slow components, respectively. 7. It was concluded that two different subtypes of LVA Ca2+ channel are present in LD neurones. Only the fast type is well expressed at the earliest postnatal stage (P12). The slow type could be found at the end of the second week (P14). The amplitude of the slow current increased progressively up to P17, obviously coinciding with dendritic expansion as judged by progressive increase of the membrane capacitance of the corresponding neurones. This property appears to differentiate neurones of the associative nuclei from neurones of other thalamic nuclei.
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PMID:Two types of low-voltage-activated Ca2+ channels in neurones of rat laterodorsal thalamic nucleus. 906 41

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


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