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Query: UMLS:C0019829 (Hodgkin's disease)
 30,247 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Teorell's fixed charge theory for membrane ion permeability was utilized to calculate specific ionic permeabilities from measurements of membrane potential, conductance, and specific ionic transference numbers. The results were compared with the passive ionic conductances calculated from the branched equivalent circuit membrane model of Hodgkin Huxley. Ionic permeabilities for potassium, sodium, and chloride of crayfish (Procambarus clarkii) medial giant axons were examined over an external pH range from 3.8 to 11.4. Action potentials were obtained over this pH range. Failures occurred below pH 3.8 during protonation of membrane phospholipid phosphate and carboxyl, and above pH 11.4 from calcium precipitation. In general, chloride permeability increases with membrane protonation, while cation permeability decreases. At pH 7.0, PK = 1.33 X 10(-5), PCl = 1.49 X 10(-6), PNa = 1.92 X 10(-8) cm/s. PK: PCl: PNa = 693:78:1. PCl is zero above pH 10.6 and is opened predominately by protonation of epsilon-amino, and partially by tyrosine and sulfhydryl groups from pH 10.6 to 9. PK is activated in part by ionization of phospholipid phosphate and carboxyl around pH 4, then further by imidazole from pH 5 to 7, and then predominately from pH 7 to 9 by most probably phosphatidic acid. PNa permeability parallels that of potassium from pH 5 to 9.4. Below pH 5 and above pH 9.4, PNa increases while PK decreases. Evidence was obtained that these ions possibly share common passive permeable channels. The data best support the theory of Teorell, that membrane fixed charges regulate permiability and that essentially every membrane ionizable group appears involved in various amounts in ionic permeability control.
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PMID:Ionic permeability of K, Na, and Cl in crayfish nerve. Regulation by membrane fixed charges and pH. 1 19

Voltage-clamp currents and resting membrane potential of squid giant axons have been studied at extracellular pH varying between 4 and 10. The membrane currents, analyzed according to the Hodgkin-Huxley equations, showed that sodium permeability, PNa(E), and potassium conductance gK(E), curves were shifted toward positive voltages by different amounts and slightly depressed as the external pH was lowered. Under the same conditions, taum(E) and taun(E) were found to be enhanced and shifted to a larger extent in the same direction. The rate constants alpham and alphan were shifted substantially toward positive voltages, but betam and betan changed hardly at all. The shift of the alpham(E) curve was analyzed in terms of a fixed surface charge model; it indicates that unspecific negative groups with an approximate pKa of 4.5 are located in the vicinity of sodium active sites with an average charge separation of 8 A. A similar figure is obtained for the potassium system from the shift of the alphan(E) curve.
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PMID:Action of extracellular pH on Na+ and K+ membrane currents in the giant axon of Loligo vulgaris. 3 97

Under depolarizing voltage clamp of Paramecium an inward calcium current developed and subsequently relaxed within 10 milliseconds. The relaxation was substantially slowed when most of the extracellular calcium was replaced by either strontium or barium. Evidence is presented that the relaxation is not accounted for by a drop in electromotive force acting on calcium, or by activation of a delayed potassium current. Relaxation of the current must, therefore, result from an inactivation of the calcium channel. This inactivation persisted after a pulse, as manifested by a reduced calcium current during subsequent depolarization. Inactivation was retarded by procedures that reduce net entry of calcium, and was independent of membrane potential. The calcium channel undergoes inactivation as a consequence of calcium entry during depolarization. In this respect, inactivation of the calcium channel departs qualitatively from the behavior described in the Hodgkin-Huxley model of the sodium channel.
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PMID:Calcium entry leads to inactivation of calcium channel in Paramecium. 10 99

A computer model of a neocortical pyramidal cell has been constructed using ideas similar to those used for hippocampal pyramidal cells. This model has been applied to the study of (a) repetitive firing, and (b) the paroxysmal depolarizing shift (PDS), an important intracellular event during seizures. Although calcium spikes have not been demonstrated directly in neocortical cells, we have postulated (by analogy with hippocampal pyramidal cells) a dendritic calcium conductance and a 'slow potassium' conductance modulated by intracellular calcium ion. With these dendritic ionic conductances, the model is able to reproduce the following experimental features of neocortical pyramidal cells: the afterdepolarization and succeeding afterhyperpolarization after an antidromic spike, and the f-I (firing rate-injected current) curve. Some of the differences between 'fast' and 'slow' pyramidal tract neurons (PTNs) -- narrower spikes and a steeper f-I curve in the fast PTNs -- may be explained by differences in Hodgkin-Huxley potassium kinetics between the two kinds of cell. The same model which faithfully reproduces repetitive firing behavior also reproduces (given appropriate synaptic inputs) the following intracellular events recording during epileptic seizures: (a) a burst of action potentials superimposed on and followed by a PDS, and (b) rapid repetitive firing succeeded by an IPSP. Thus, a single set of parameters can reporduce both normal physiological behavior and 'epileptic' behavior: the particular behavior seen depending on how the cell is stimulated. This overall result is the same as for our model of the CA1 hippocampal cell. It suggests that certain acutely acting epileptogenic agents, e.g. penicillin, may act by increasing synaptic input (perhaps both excitatory and inhibitory) to pyramidal cells, rather than by altering their membrane properties. As in our CA1 hippocampal cell model, bursting seems to be a phenomenon generated by the apical dendrite.
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PMID:Neocortical pyramidal cells: a model with dendritic calcium conductance reproduces repetitive firing and epileptic behavior. 22 13

We present a novel recursion method for obtaining theoretical expressions for unidirectional single-file fluxes of ions through narrow membrane channels containing an arbitrary number of ion sites. The theory is applied to experimental tracer fluxes associated with nerve impulses from cephalopod giant axon membranes at various temperatures between 7 degrees and 27 degrees. The comparison between the theoretical and experimental one-way fluxes suggests that the potassium channel in nerve membrane contains three ion sites, which is consistent with the deduction by Hodgkin and Keynes that the potassium channel contains two or three sites on the basis of the ratio of tracer influx to tracer efflux. The analytical results in this paper provide a further test of the single-file model for nerve and other membrane preparations.
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PMID:Random walk analysis of potassium fluxes associated with nerve impulses. 27 79

1. The spontaneous electrical activity of small strips of muscle from the sinus venosus region of the heart of Rana catesbeiana was investigated using the double sucrose gap technique. The voltage clamp was used to record the ionic currents underlying the pace-maker depolarization and the action potential.2. The records of spontaneous electrical activity are very similar to those obtained from the sinus venosus using micro-electrodes. Moreover, the pace-maker activity is almost completely insensitive to tetrodotoxin (TTX) at 2.0 x 10(-6) g/ml., which suggests that the pace-maker responses can be classified as primary, as opposed to follower pacing.3. In response to short rectangular depolarizing voltage clamp pulses, only one inward current is activated. This current is almost completely insensitive to TTX but can be blocked by manganese ions. It appears, therefore, to be equivalent to the slow inward (Ca(2+)/Na(+)) current, I(si), of other cardiac tissues. The threshold for I(si) is near to the maximum diastolic potential, indicating that it must be activated during the pace-maker depolarization.4. Interruption of the normal pace-maker depolarization by rapid activation of the voltage clamp circuit reveals the time-dependent decay of outward current. This current reverses between -75 and -90 mV and, therefore, is probably carried mainly by potassium ions.5. Outward current decay is not a simple exponential, and Hodgkin-Huxley analysis suggests that two distinct components of outward current may be present. One of these is activated in the potential range of the pace-maker depolarization and the other at more positive potentials. Both outward currents reach full, steady-state activation at about zero mV, i.e. within the ;plateau' range of the sinus action potential.6. These results are compared with other recently published voltage clamp data from the rabbit sino-atrial node.7. A hypothesis for the generation of pace-maker activity is presented which involves (i) decay of outward current and (ii) activation of the slow inward current, I(si).
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PMID:Membrane currents underlying activity in frog sinus venosus. 30 99

1. The concentrations of sodium, potassium and chloride in frog and bovine lenses showed a normal intracellular ion distribution with the sum of the internal cations approximately equal to the external sum. In the cephalopod lens, however, the sum inside was much lower than that outside.2. The membrane potentials of frog, Sepiola and bovine lenses were -63, -63 and -23 mV respectively. A comparison of the electrical data with the Nernst potentials predicted from ion concentration data indicated that sodium and chloride ions as well as potassium contributed to the membrane potential in frog and bovine. In contrast, the membrane and Nernst potentials for potassium were equal in Sepiola.3. Substituting potassium for sodium in the external medium depolarized lens potentials in all three species. Estimates of the relative permeabilities of sodium, potassium and chloride were obtained by fitting the Goldman-Hodgkin-Katz equation to the potential data.4. The potassium permeability was determined directly by (42)K efflux measurements and values of 2.99, 9.83 and 3.13 (x (-8) m sec(-1)) were obtained for frog, Sepiola and bovine lenses respectively.5. The effect of raising external potassium on the efflux rate constant was determined and there was reasonable agreement between experiment and theory (Kimizuka-Koketsu) in frog and bovine lenses, but the Sepiola data indicated that the potassium permeability decreased by a factor of 2.6 when the external potassium was raised from 10 to 120 mM-K+.6. The measured specific conductances, obtained using two internal micro-electrodes, were 7.7, 15.9 and 9.9 (Sm(-2)) for frog, cephalopod and bovine lenses respectively. These data compare with computed values (Kimizuka-Koketsu theory) of 7.5, 14.1 and 17.2 (Sm(-2)).7. The effect of increasing external potassium on the conductance was also tested and there was good agreement between experiment and theory (assuming constant permeabilities) only in the amphibian lens. However, when the cephalopod data were corrected assuming a 2.6-fold decrease in P(K) for a twelvefold increase in potassium, then there was excellent agreement between experiment and theory.8. The bovine measured conductances were much lower than the theoretical values throughout the range of external potassium concentrations and several explanations were proposed to account for the discrepancies.
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PMID:A comparison of ion concentrations, potentials and conductances of amphibian, bovine and cephalopod lenses. 30

1. Kinetics of inactivation of sodium channels in myelinated nerve from Rana pipiens were studied at 4.5 degrees C using the voltage clamp technique of Dodge & Frankenhaeuser (1958).2. Potassium currents were blocked by cutting the internodes in 20 mM-TEA-Cl + 100 mM-KCl and by adding 12 mM-TEA-Cl to the external Ringer. Leakage and capacitative currents were subtracted electronically.3. Kinetics of recovery from inactivation of the sodium channels were studied by inactivating the channels with a large depolarizing prepulse and allowing the channels to recover at different potentials; the extent of recovery was measured by applying a test pulse at various times after the prepulse.4. Kinetics of development of inactivation were studied by two different methods. The first was to measure the decay of sodium current under a maintained depolarization. The second method was to measure the decay of the peak sodium current in a test pulse as a function of time after the onset of a maintained depolarization. These two methods yielded similar results for the kinetics of inactivation development.5. Contrary to expectations of the Hodgkin-Huxley formalism, the time course of recovery from and development of inactivation is not strictly exponential. Rather, recovery from complete inactivation shows an initial delay which depends on recovery potentials. Development of inactivation at a fixed potential exhibits at least two exponentials.6. The steady-state inactivation curve h(infinity)(E) is asymmetrical and is fitted better by 1/[1+exp (A(1)E+B(1)) +exp (A(2)E+B(2))] than by 1/[1+exp (AE+B)].7. Most of the above kinetic observation on inactivation can be fitted by the following modification of the h system of the Hodgkin-Huxley formalism: [Formula: see text]8. In the analysis it was not necessary to modify the concept of two separate processes, activation and inactivation, governing the opening and closing of the sodium channels.
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PMID:Inactivation of sodium channels: second order kinetics in myelinated nerve. 30 88

1. Voltage-clamp studies were carried out on single rabbit myelinated nerve fibres at 14 degrees C with the method of Dodge & Frankenhaeuser (1958). 2. A method was developed to allow the ionic currents through the modal membrane to be calibrated exactly under voltage-clamp conditions by measuring the resistance of the internode through which the current was injected. 3. The ionic currents in a rabbit node of Ranvier can be resolved into two components, a sodium current and a leak current. Potassium current is almost entirely absent. 4. The sodium currents in rabbit nodes were fitted by the Hodgkin-Huxley model using m2h kinetics. The kinetics of sodium currents in a rabbit node differ from that in a frog node under similar experimental conditions in two respects: (a) inactivation is faster, tau h for rabbit being 2-3 times smaller around -50 mV; (b) the P(Na) (E) curve for mammal is shifted 10-15 mV in the hyperpolarizing direction. 5. From the kinetics of sodium current, the non-propagating rabbit action potential was reconstructed at 14 degrees C. The transient inward sodium current is responsible for the fast initial depolarization phase of the action potential, while the repolarizing phase is accounted for by leak alone. The computed shape of the action potential was in good agreement with the experimentally obtained action potential. 6. At 14 degrees C, frog and rabbit nodes with similar diameters have similar measured gNa values.
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PMID:A quantitative description of membrane currents in rabbit myelinated nerve. 31 74

A nerve membrane model with a two-state pore system was investigated by computer simulation in the uniform (space-clamped) case. Both sodium and potassium conducting pores were modelled, each pore having four independent gates which switched randomly between the open and the closed position, governed by the assumed rate constants. Each pore conducted only when all the gates were open. The model was based upon the Hodgkin-Huxley equations for the giant axon in squid, and in the limit of an infinite number of pores it was identical to these. The firing behaviour of this model as a function of the number of pores and the injected current were investigated. The mean firing frequency and the distribution of interspike intervals were mainly used in the presentation of the results. It was found that for pore numbers less than about 20 000 the main effects due to a finite number of pores were a lowering of the current threshold for firing and a more linear frequency current relationship relative to that of the original H-H equations. For higher pore numbers an increase in the current threshold and a pronounced burst firing close to the threshold were found.
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PMID:Firing behaviour in a stochastic nerve membrane model based upon the Hodgkin-Huxley equations. 54 28


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