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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 study in voltage clamp conditions of the modifications of the cardiac membrane conductances by quinidine sulfate has been carried out on frog atrial fibers by means of the double sucrose gap technique. The computation of the parameters related to the conductances has been done according to the Hodgkin and Huxley mathematical model proposed in 1952. The computed conductances concern the sodium conductance, the calcium conductance, and the total delayed conductance. A decrease of all of the studied conductances is observed in the presence of quinidine sulfate. This drug also mainly induced a slowing down of several activation, inactivation, and reactivation kinetics. The results obtained allow a more detailed explanation of the mechanism of action of quinidine sulfate in the membrane. Although quinidine is known to possess antiarrhythmic properties, the exact mechanisms of its action are not clear. The present study was therefore undertaken to provide some information on this point.
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PMID:Effects of antiarrhythmic drugs on cardiac membrane conductances; a study using the Hodgkin and Huxley mathematical model. 108 Dec 53

The electrical behavior of small single frog atrial trabeculae in the double sucrose gap has been investigated. The currents injected during voltage clamp experiments did not behave as predicted from the assumption of spatial uniformity of the voltage across a Hodgkin-Huxley membrane. Much of the difference is due to the geometrical complexities of this tissue. Nonetheless, two transient inward currents have been identified, the faster of which is blocked by tetrodotoxin (TTX). The magnitude of the slower transient varies markedly between preparations but always increases in a given preparation with increase of external calcium. The fast transient current traces, at small to intermediate depolarizations, are often marred by the presence of notches and secondary peaks due most probably to the loss of space clamp conditions. In many preparations these could be removed by reducing the current magnitude through application of a partially-blocking dose of TTX. Conversely, in the preparations whose fast transient was fully blocked by TTX, notches and secondary peaks in the slow transient could by induced through increasing calcium concentration and thereby the slow current magnitude. Previously used techniques for the measurement of the reversal potential of the fast inward transient have been shown to be invalid. In so far as they can be measured, the reversal potentials of the fast and slow inward transient are in the same neighborhood, i.e. around 120 mV from rest. The true values may be quite a bit apart. The total charge flow in the capacitive transient was measured for different sized nodes and preparations. From these data and estimates of plasma membrane area per unit trabecular volume, specific membrane capacitances of around 3 muF/cm2 were calculated for small bundles. The apparent ion current densities on this basis are approximately 1/10 of those measured in axons. The capacitive current occurring in small bundles decayed as the sum of at least three exponential functions of time. On the basis of these data and the anomalously large stable node widths, we suggest a coaxial core model of the preparation with the inner elements in series with an additional large extracellular resistance.
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PMID:Electrical characteristics of frog atrial trabeculae in the double sucrose gap. 108 89

1. Helix aspersa neurones under voltage clamp generate prolonged outward currents (potassium currents) in response to depolarizing command pulses. 2. The potassium currents recorded from cell A were reversibly reduced 25-50% by 10 mM cobalt ions in the bathing medium; 1 mM lanthanum, 10(-6) g/ml. D-600 and 10(-6) g/ml. iproveratril had similar effects but were only partially reversible. 3. The relationship between the potassium currents and the membrane potential had an "n" shape in normal saline. In calcium-free saline (containing 25 mM magnesium) the potassium currents were reduced and the "n" shape was abolished. The effect of calcium-free saline was readily reversible. 4. The voltage-dependence of the calcium-sensitive potassium currents was similar to that of the "late" calcium channel in squid axons (Baker, Hodgkin & Ridgway, 1971). 5. When cell A was depolarents were made up of two exponentially declining components. The slower of the two components was reduced in calcium-free saline. 6. When cell A was depolarized by 150 mV for 10 msec and then repolarized the "tail" currents were made up of a single rapidly declining component. The reversal potential of this component changed by 58 mV for a tenfold change in the external potassium concentration as predicted by the Nernst equation. 7. The reversal potential of "tail" currents having both components was less sensitive to changes in the external potassium concentration. 8. Tetraethylammonium (TEA) ions blocked both calcium dependent and voltage sensitive potassium currents. Each receptor was found to bind a single molecule of TEA. The dissociaton constant was about 10 mM in each case. 9. The intracellular concentration of ionized calcium was estimated from the potential at which there was no apparent calcium influx (the null point). It was between 3 x 10(-8) M and 8 x 10(-8) M with 10(-2) M calcium in the bathing medium. 10. The null point changed 30 mV for a tenfold change in the external calcium concentration as predicted by the Nernst equation. 11. It is concluded that depolarization of Helix neurones activates two typesof potassium channel. One channel is voltage dependent and highly selective for potassium. Activation of the other channel is dependent on the influx (or injection, see Meech, 1972, 1974a) of calcium. This calcium mediated potassium activation system saturates at high external calcium concentrations and is inhibited by external magnesium ions.
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PMID:Potassium activation in Helix aspersa neurones under voltage clamp: a component mediated by calcium influx. 117 91

Ionic currents in heart muscle are usually described in terms of the Hodgkin-Huxley theory for nerve fibers. Attention is paid to some aspects of the sodium and calcium conductance which seem to be specific for heart muscle: 1) recent findings indicate that repriming of the sodium and calcium conductance in heart muscle cannot be described as the reverse process of inactivation; 2) the existence of an important calcium current is well established, but controversial findings have been obtained for the time constant of inactivation; 3) Na and Ca interact in determining the slow channel current. Depending on the external Na and Ca concentration, antagonistic as well as synergistic effects may be obtained. An explanation is offered for these contradictory results.
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PMID:The ionic basis of membrane excitation in ordinary myocardial fibers: some aspects of the sodium and calcium conductance. 118 61

1. Giant axons from the squids Dosidicus gigas, Loligo forbesi and Loligo vulgaris were internally perfused with 550 or 275 mM KF plus sucrose and bathed in artificial sea water containing 45Ca, 28Mg or mixtures of 45Ca-28Mg or 45Ca-22Na. Resting influxes and extra influxes during voltage-clamp pulses were measured by collecting and counting the internal perfusate. 2. For Dosidicus axons in 10 mM-CaCl2 the resting influx of calcium was 0-016 +/- 0-007 p-mole/cm2 sec and a linear function of external concentration. For two experiments in 10 and 84-7 mM-CaCl2, 100 nM tetrodotoxin had no effect. Resting calcium influx in 10 mM-CaCl2 was 0-017 +/- 0-013 p-mole/cm2 sec for Loligo axons. 3. With 55 mM-MgCl2 outside the average resting magnesium influx was 0-124 +/- 0-080 p-mole/cm2 sec for Loligo axons. Discarding one aberrant point the value is 0-105 +/- 0-046 which is not significantly different from the resting calcium influx for Dosidicus fibres in 55 mM-CaCl2, given as 0-094 p-mole/cm2 sec by the regression line shown in Fig. 1. In two experiments 150 nM tetrodotoxin had no effect. 4. With 430 mM-NaCl outside 100 nM tetrodotoxin reduced the average resting influx of sodium in Dosidicus axon from 27-7 +/- 4-5 to 25-1 +/- 6-2 p-mole/cm2 sec and for Loligo fibres in 460 mM-NaCl from 50-5 +/- 4 to 20 +/- 8 p-mole/cm2 sec. 5. Using depolarizing pulses of various durations, the extra calcium influx occurred in two phases. The early phase was eliminated by external application of tetrodotoxin. The results of analysis are consistent with, but do not rigorously demonstrate, the conclusion that the tetrodotoxin sensitive calcium entry is flowing through the normal sodium channels (cf. Baker, Hodgkin & Ridgway, 1971). 6. Measurements of extra influxes using 22Na and 45Ca simultaneously indicate that the time courses of tetrodotoxin sensitive calcium and sodium entry are similar but not necessarily identical. It is very doubtful that any significant calcium entry occurs before the sodium or is involved in the activation of the sodium system. 7. These measurements confirm for Loligo, as previously shown for Dosidicus axons, that the magnitude and time course of the sodium entry during a depolarizing pulse deduced from electrical measurements is the same as that measured with 22Na. 8. Using 28Mg, or mixtures of 45Ca and 28Mg, we observed a single phase of magnesium entry which was insensitive to external tetrodotoxin or internal tetraethyl ammonium. The magnitude of the magnesium influx was considerably greater than the calcium extra entry and large enough to have been detected in the experiments of Meves & Vogel (1973) if it represented current. 9. We suggest the possibility that the calcium and magnesium extra influxes, after external treatment with tetrodotoxin, during a depolarizing pulse, do not contribute to the measured current.
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PMID:Simultaneous measurements of magnesium, calcium and sodium influxes in perfused squid giant axons under membrane potential control. 120 93

We describe a kinetic reaction sequence for the sodium conductance system in the squid axon. It closely matches the original Hodgkin and Huxley model for voltage clamp experiments but it generates an action potential without a bump on the falling phase. When calcium ions are included in the reaction, this model faithfully reproduces the experimental observations of Frankenhaeuser and Hodgkin on the effects of altered calcium in the medium. The fit to experiment is much better than when a voltage shift in rate constants is assumed. The gating currents recently observed by Armstrong and Bezanilla are not compatible with the Hodgkin and Huxley model but can be reprocuced in considerable detail by the kinetic model. Thus it appears that the kinetic model differs from that of Hodgkin and Huxley perhaps in an important and fundamental way that makes it more realistic.
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PMID:A kinetic model for the sodium conductance system in squid axon. 124 46

67Ga is known to concentrate in the breasts of pregnant and postpartum women, and a case is now described in which 67Ga uptake was seen in the breasts of a woman who was neither pregnant nor postpartum, but was receiving chemotherapy for Hodgkin's disease. Comparative studies of the uptake of 67Ga and 45Ca in lactating dogs have shown that both nuclides are secreted in the milk in similar amounts and in protein-bound form. The concentration of 67Ga in mammary tissue is about one-half of that found in the milk at 5 hr postinjection but, by 48 hr, the concentrations are approximately equal. There were similarities in the subcellular distributions of 67Ga and 45Ca in the lactating mammary gland at 5 and 48 hr. Although there was a correlation between 67Ga and 45Ca in individual pieces of a lactating mammary gland at 5 hr after injection, no such correlation was seen between the two nuclides in multiple samples of a transmissible venereal tumor measured at various time intervals. The rate of dispersion of 67Ga and 45Ca from the lactating mammary gland was similar but, in the tumor, 67Ga was present in very much greater amounts than 45Ca and was retained longer. It is concluded that, although there may be similarities in the metabolic pathways of gallium and calcium in the lactating mammary gland, there is no similarity in the mechanism of uptake of these two elements into tumors.
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PMID:The concentration of 67Ga and 45Ca in the lactating mammary gland and its relevance to the tumor uptake of 67Ga citrate. 126 Jul 45

1. To perform simulations of the various modes of action potential generation in thalamic relay neurons, we developed Hodgkin-and-Huxley style mathematical equations that describe the voltage dependence and kinetics of activation and inactivation of four different currents, including the transient, low-voltage-activated Ca2+ current (IT), the rapidly inactivating transient K+ current (IA), the slowly inactivating K+ current (IK2), and the hyperpolarization-activated, mixed cationic current (Ih). The modeled currents were derived either from acutely dissociated rat thalamic relay neurons (IT, IA, IK2), or from guinea pig thalamic relay cells maintained in slices in vitro (Ih). 2. The voltage dependence of steady-state activation and inactivation of IT, IA, and IK2 and the activation of Ih could be modeled with Boltzmann-style equations. Modeling of the behavior of IT to depolarizing steps in voltage clamp required the use of the constant field equation to relate permeability to T-current amplitude. The time constant of activation of IT was described by a continuous bell-shaped function with a maximum near 15 ms at threshold for activation (-75 mV) and 23 degrees C. Mathematical description of the kinetics of inactivation and removal of inactivation of this current required two separate functions. 3. The rapidly activating and inactivating K+ current IA was modeled by assuming two components with different time constants of inactivation. The kinetics of activation was described as a continuous function of voltage with the slowest time constant, near 2.5 ms, at threshold for activation (-60 mV) and 23 degrees C. In contrast, the kinetics of inactivation of both components were described as voltage independent, consistent with experimental data. The rate or removal of inactivation of both components of IA was described as continuously increasing with the degree of hyperpolarization. 4. The slowly inactivating K+ current IK2 was also modeled by assuming two components with different rates of inactivation. The kinetics of activation were described by a bell-shaped function with a maximum time constant near 80 ms at -40 mV and 23 degrees C, whereas threshold for activation was approximately -60 mV. Inactivation of both components was modeled as relatively independent of voltage, whereas removal of inactivation was described as a continuous function of membrane potential. 5. The hyperpolarization-activation cationic current, Ih, was modeled by assuming that the current activates with a single exponential relation and does not inactivate.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Simulation of the currents involved in rhythmic oscillations in thalamic relay neurons. 127 35

1. Whole-cell K+ currents contributing to the resting membrane potential and repolarization of the action potential were studied in voltage-clamped parasympathetic neurones dissociated from neonatal rat intracardiac ganglia and maintained in tissue culture. 2. Rat intracardiac neurones had a mean resting membrane potential of -52 mV and mean input resistance of 850 M omega. The current-voltage relationship recorded during slow voltage ramps indicated the presence of both leakage and voltage-dependent currents. The contribution of Na+, K+ and Cl- to the resting membrane potential was examined and relative ionic permeabilities PNa/PK = 0.12 and PCl/PK < 0.001 were calculated using the Goldman-Hodgkin-Katz voltage equation. Bath application of the potassium channel blockers, tetraethylammonium ions (TEA; 1 mM) or Ba2+ (1 mM) depolarized the neurone by approximately 10 mV. Inhibition of the Na(+)-K+ pump by exposure to K(+)-free medium or by the addition of 0.1 mM ouabain to the bath solution depolarized the neurone by 3-5 mV. 3. In most neurones, depolarizing current pulses (0.5-1 s duration) elicited a single action potential of 85-100 mV, followed by an after-hyperpolarization of 200-500 ms. In 10-15% of the neurones, sustained current injection produced repetitive firing at maximal frequency of 5-8 Hz. 4. Tetrodotoxin (TTX; 300 nM) reduced, but failed to abolish, the action potential. The magnitude and duration of the TTX-insensitive action potential increased with the extracellular Ca2+ concentration, and was inhibited by bath application of 0.1 mM Cd2+. The repolarization rate of the TTX-insensitive action potential was reduced, and after-hyperpolarization was replaced by after-depolarization upon substitution of internal K+ by Cs+. The after-hyperpolarization of the action potential was reduced by bath application of Cd2+ (0.1 mM) and abolished by the addition of Cd2+ and TEA (10 mM). 5. Depolarization-activated outward K+ currents were isolated by adding 300 nM TTX and 0.1 mM Cd2+ to the external solution. The outward currents evoked by step depolarizations increased to a steady-state plateau which was maintained for > 5 s. The instantaneous current-voltage relationship, examined under varying external K+ concentrations, was linear, and the reversal (zero current) potential shifted in accordance with that predicted by the Nernst equation for a K(+)-selective electrode. The shift in reversal potential of the tail currents as a function of the extracellular K+ concentration gave a relative permeability, PNa/PK = 0.02 for the delayed outward K+ channel(s).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Resting membrane potential and potassium currents in cultured parasympathetic neurones from rat intracardiac ganglia. 128 80

We investigated the effects of cAMP-dependent phosphorylation on the voltage- and time-dependent gating properties of Ca2+ channel currents recorded from bovine adrenal chromaffin cells under whole-cell voltage clamp. Extracellular perfusion with the membrane-permeant activator of cAMP-dependent protein kinase, 8-bromo(8-Br)-cAMP (1 mM), caused a 49%, 29%, and 21% increase in Ca2+ current (ICa) amplitudes evoked by voltage steps to 0, +10, and +20 mV respectively (mean values from eight cells, p less than or equal to 0.05). Analysis of voltage-dependent steady-state activation (m infinity) curves revealed a 0.70 +/- 0.27 charge increase in the activation-gate valency (zm) following 8-Br-cAMP perfusion. Similar responses were observed when Ba2+ was the charge carrier, where zm was increased by 1.33 +/- 0.34 charges (n = 8). The membrane potential for half activation (V1/2) was also significantly shifted 6 mV more negative for IBa (mean, n = 8). The time course for IBa (and ICa) activation was well described by second-order m2 kinetics. The derived time constant for activation (tau m) was voltage-dependent, and the tau m/V relation shifted negatively after 8-Br-cAMP treatment. Ca2+ channel gating rates were derived from the tau m and m infinity 2 values according to a Hodgkin-Huxley type m2 activation process. The forward rate (alpha m) for channel activation was increased by 8-Br-cAMP at membrane potentials greater than or equal to 0 mV, and the backward rate (beta m) decreased at potentials less than or equal to + 10 mV. Time-dependent inactivation of ICa consisted of a slowly decaying component (tau h approximately 300 ms) and a "non-inactivating" steady-state component. The currents contributed by the two inactivation processes displayed different voltage dependences, the effects of 8-Br-cAMP being exclusively on the slowly inactivating L-type component.
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PMID:Cyclic AMP-dependent phosphorylation modifies the gating properties of L-type Ca2+ channels in bovine adrenal chromaffin cells. 131 68


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