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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

1. Sodium currents (INa) and asymmetrical displacement currents (ID) were measured in the same nerve fibres from Rana esculenta under similar conditions. 2. For exploring possible kinetic and steady state relations between INa and ID the following quantities were compared: (i) the activation of the sodium channels and (ii) the charge displacement of ID. 3. The delay of sodium activation increased after hyperpolarization. A corresponding effect on the displacement of charge was not observed. 4. Upon a small depolarization sodium activation rose slower than the displacement of charge, whereas at large depolarizations sodium activation reached a steady level before the charge displacement. 5. Upon repolarization to various levels between -52 and 12 mV relative to the resting potential, the ratio between the time constants of charge displacement and of sodium tail current varied between 3 and 1. 6. In the steady state the sodium activation was one half at about the same potential as the charge displacement but exhibited a clearly steeper voltage dependence. 7. Blocage of sodium channels with tetrodotoxin did not affect the asymmetrical displacement current. Replacing a part of external Na by tris did not alter the sodijm activation process. 8. The results indicate that the asymmetrical displacement of charge may reflect states of the gating mechanism in sodium channels but cannot be considered as a correlate of the Hodgkin Huxley m variable.
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PMID:Asymmetrical displacement current and its relation with the activation of sodium current in the membrane of frog myelinated nerve. 108 37

A variety of experimental observations in Myxicola and other preparations indicate that the sodium conductance, gNa, has properties quite different from those described by the m and h variables of Hodgkin and Huxley. A new quantitative description of the gNa is presented in which the gNa is assumed to be proportional to the fifth power of a generalized second-order variable, i.e., gNa = g'Na times v to the fifth, v = -Kav + K2U = K3, U = K4U + K5v + K6. This model is shown to be able to quantitatively simulate all of the experimentally observed behavior of the gNa. A view of the sodium gate consistent with these kinetics is to imagine it to be composed of five independent subunits, each of the type A eq. B eq. C eq. A where A represents the resting state, B the conducting state, and C the inactivated state. A model in which the subunit is of the type A eq. B eq. C could not simulate the experimental observations. It was concluded that two processes are sufficient to account for all of the behavior of the gNa.
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PMID:Quantitative description of the sodium conductance of the giant axon of Myxicola in terms of a generalized second-order variable. 111 31

The normal resting potential of the rabbit lens, -70mV, is altered to -59mV by ouabain concentrations up to 5-1- minus 6M, and to -52mV at 4 degrees C. Ouabain acts only at the anterior lens surface. The temperature effect id completely reversible. The Hodgkin-Katz-Goldman equation can be used with the measured lens potentials and Na+ and K+ levels in the lens and bathing medium to obtain alpha, the ration of the membrane permeabilities to Na+ and K+. The alpha-values obtained were 0.052 at 4 degrees C and 0.053 in 5-10 minus 6M ouabain. These data suggest that the change in potential due to cold and ouabain is caused by an inhibition of an electrogenic Na+ ump in the anterior lens epithelium.
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PMID:An electrogenic component of the potential difference in the rabbit lens. 112 14

In this paper we explore the properties of a mathematical model for the passive sodium permeability system of excitable membranes. This model is distinguished by the explicit inclusion of a rate constant which depends not on instantaneous voltage, but on rate of voltage change. Actually, the model is a rather modest modification of the Hodgkin-Huxley model, but displays some behaviors which the H-H model does not. Among these behaviors are a pronounced inactivation shift (for certain parameter values), a difference between inactivation time constant as measured by turning off a sodium current under sustained depolarization and as measured by double pulse experiments, skip runs under sustained current stimulation, and accommodation to slowing rising currents.
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PMID:A transient excited state model for sodium permeability changes in excitable membranes. 114 60

1. The electrical activity of Cardiac Purkinje fibres was reconstructed using a mathematical model of the membrane current. The individual components of ionic curent were described by equations which wee based as closely as possible on previous experiments using the voltage clamp technique. 2. Membrane action potentials and pace-maker activity were calculated and compared with time course of underlying changes in two functionally distinct outeard currents, iX1 and iK2. 3. The repolarization of the theoretical action potential is triggered by the onset of iX1, which becomes activated over the plateau range of potentials. iK2 also activates during the plateau but does not play a controlling role in the repolarization. Hwever, iK2 does govern the slow pace-maker depolarization through its subsequent deactivation at negative potentials. 4. The individual phases of the calculated action potential and their 'experimental' modifications were compared with published records. The upstroke is generated by a Hodgkin-Huxley type sodium conductance (gNa), and rises with a maximum rate of 478 V/sec, somewhat less than experimentally observed values ( up to 800 V/sec). The discrepancy is discussed in relation to experimental attempts at measuring gNa. 5. The ole of the transient outward chloride current (called igr) was studied in calculations of the rapid phase of repolarization and 'notch' configuration...
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PMID:Reconstruction of the electrical activity of cardiac Purkinje fibres. 118 7

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

Trinitrophernol (TNP) selectively alters the sodium conductance system of lobster giant axons as measured in current clamp and voltage clamp experiments using the double sucrose gap technique. TNP has no measurable effect on potassium currents but reversibly prolongs the time-course of sodium currents during maintained depolarizations over the full voltage range of observable currents. Action potential durations are increased also. Tm of the Hodgkin-Huxley model is not markedly altered during activation of the sodium conductance but is prolonged during removal of activation by repolarization, as observed in sodium tail experiments. The sodium inactivation versus voltage curve is shifted in the hyperpolarizing direction as is the inactivation time constant curve, measured with conditioning voltage steps. This shift speeds the kinetics of inactivation over part of the same voltage range in which sodium currents are prolonged, a contradiction incompatible with the Hodgkin-Huxley model. These results are interpreted as support for a hypothesis of two inactivation processes, one proceeding directly from the resting state and the other coupled to the active state of sodium conductance.
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PMID:Selective modification of sodium channel gating in lobster axons by 2, 4, 6-trinitrophenol: Evidence for two inactivation mechanisms. 119 89

The question of calculating excitation propagation velocity is analyzed on the basis of the Hodgkin-Huxley model. The activation of the sodium current is assumed to be rapid as compared to the rate of potential variation. Because of slow variation of potassium activation and sodium inactivation the dynamics of these processes is assumed to be of negligible effect in the region of impulse velocity formation. By means of pieace-wise linear approximation of thus obtained voltage-current characteristics the characteristics the analytical solution of the problem was found. In two limiting cases this solution coincides with the solutions of Kolmogorov and Scott. The dependence of impulse velocity on parameters is analyzed and illustrated graphically.
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PMID:[Rate of excitation propagation in a reduced Hodgkins-Huxley model. I. Rapid relaxation of the sodium current]. 120 3

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


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