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

Differentiation of membrane channel models based on fluctuation (or noise) analysis is discussed. The theory is particularly useful in distinguishing a single-conductance model (Hodgkin-Huxley formalism) from a multiconductance model. When applied to the frog node of Ranvier, it seems likely that the potassium channels of the membrane may have multiconductance states.
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PMID:Differentiation of channel models by noise analysis. 93 34

1. Muscle fibres from goats with myotonia congenita show characteristic responses to stimulation with intracellular currents (Adrian & Bryant, 1974). To test whether the reduced surface chloride conductance can account for these myotonic discharges, we have calculated responses of a model 'muscle fibre' to intracellular current of long duration (greater than 100 msec), assuming that the current is applied at the end of the fibre, that the fibre is of finite length, that a regenerative action potential occurs in the transverse tubular system as well as the surface, and that the potassium current in the wall of the transverse tubular system raises the potassium in the tubular lumen. In the absence of information about the kinetic parameters of the ionic currents in mammalian muscle we have used numerical values from frog muscle (Adrian, Chandler & Hodgkin, 1970). 2. In calculations with a normal surface chloride conductance a long maintained current gives only one action potential. Reduction of the chloride conductance to a half produces repetitive firing during the current; reduction to a tenth produces repetitive firing during and a small number of action potentials after the end of the current. Elimination of the tubular potassium accumulation from the calculation reduces the number but does not eliminate action potentials arising after the end of the applied current. 3. With a tenth of the normal chloride conductance calculated responses show maintained firing following a constant current if the deactivating rate of the sodium channels (betam) is reduced by 25%. As before, eliminating potassium accumulation reduces the number of post-stimulus action potentials, but it does not eliminate them altogether. 4. We conclude that in the absence of a surface chloride conductance tubular potassium accumulation could certainly contribute to the instability of the membrane, but it is clear that potassium accumulation is not the only reason for the instability of myotonic muscle fibres. The kinetics of the sodium channels are important and we do not know that they are the same in normal and myotonic fibres. Nevertheless the presence of a surface chloride conductance does stabilize the response of a fibre to constant current or to repetitive stimulation, and its absence could be a sufficient condition for myotonic behaviour.
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PMID:Action potentials reconstructed in normal and myotonic muscle fibres. 94 49

1. Theoretical computations were conducted on a computer model of a segmented, nonhomogeneous axon to understand the mechanism of frequency block of conduction. 2. The model is based on the Hodgkin-Huxley equations modified in several ways to better describe the cockroach axon. We used cockroach parameters where available. 3. The increase in fiber radius was spread over a series of segments to approximate a taper. We found that a taper allows a larger overall increase in fiber diameter than a single step to be successfully passed. 4. We studied effects on a train of impulses. The modified equations included effects due to changes in extracellular potassium concentration resulting from the repetitive firing of the axon. 5. An increase in diameter which allows a single spike to pass blocks the subsequent impulses in a train at the taper if potassium concentration variability is introduced. This could explain the low-pass filter characteristics of axon constrictions. 6. Results of the model fit well with the experiemental spike shape and height. Data were computed for the refractory period and its dependence on the taper parameters.
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PMID:Theoretical analysis of parameters leading to frequency modulation along an inhomogeneous axon. 96 45

The ionic channels in excitable membranes are of two classes: those that open and close when the membrane potential alters and those that respond to the release of an appropriate chemical transmitter. The former are responsible for the conduction of impulses in nerve and muscle fibres and the latter for synaptic transmission. It is now clear that the sodium and potassium channels in electrically excitable membranes are functionally distinct, since each can be blocked without affecting the behaviour of the other. It has recently proved possible to study, in the voltage-clamped squid giant axon, the movements of the mobile charges or dipoles that form the voltage-sensitive portion of the sodium channels, which give rise to the so-called 'gating' current. Detailed comparisons can now be made between the kinetics of the ionic conductances as described by Hodgkin & Huxley, and the steady-state distribution and kinetics of the charged controlling particles, which should lead to useful conclusions about the intramolecular organization of the sodium channels and the conformational changes that take place under the influence of the electric field. There is as yet little information about the chemical nature of the electrically excitable channels, but significant progress has been made towards the isolation and characterization of the acetylcholine receptors in muscle and electric organ.
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PMID:The ionic channels in excitable membranes. 104 Dec 42

1. Voltage clamp experiments were carried out on frog myelinated fibres to study the origin of the transient inward current occuring when the membrane is repolarized after long lasting depolarizing pulses (tail current denominated "Ip" by Frankenhaeuser). 2. The "tail" of inward current measured during repolarization after break of the depolarizing pulse is insensitive to external application of TTX, is abolished by external treatment with TEA or Cs and decreases when the outward K-current during the pulse is diminished. 3. The time course of the "tail" current is exponential. Its direction depends on the duration of the depolarizing pulse and on the membrane potential level at repolarization. 4. It is concluded that the tail of inward current during repolarization is carried by K-ions accumulated in the perinodal space during a depolarizing pulse. The data suggest that the tail reflects the time course of the restoration of the K-concentration to its initial level. The tail current itself contributes to this restoration depending on the Em value at repolarization. 5. It is shown that one of the two phenomenological models proposed by Frankenhaeuser and Hodgkin to account for the external potassium accumulation observed in the squid giant axon may be also applied to the Ranvier node. Assuming that the thickness of the space is 2900 A and that the K-permeability of the barrier is 0.019 cm/sec, it is possible to account for the observed changes in [K]0 during a long lasting depolarizing pulse. 6. The existence of such a barrier would introduce an electrical resistance in series with the nodal membrane of roughly 150 000 omega.
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PMID:Potassium accumulation in the perinodal space of frog myelinated axons. 108 77

The kinetics of potassium conductance changes were determined in the voltage clamped frog node (Rana esculenta), as a function of conditioning prepotential. The conditioning potential duration varied from 1 to 50 ms and the amplitude between -60 and +130 mV (relative to rest). The conductance kinetics were determined at a single test potential of +20 mV (depolarization) by means of the slope of log [ninfinity - nt] vs. time relationship which defines the time constant of the process (tau). The values of tau, after conditioning hyperpolarizations, were around 5 ms, up to 10 times greater than values obtained following a strong depolarization. The tau vs. pre-potential curve was sigmoid in shape. These differences were only slightly dependent on [K+]0 or conditioning pulse duration. The steady-state current values were also found to be a function of conditioning potential. After conditioning hyperpolarizations, the log [ninfinity - nt] vs. time curve could not be fitted by a single exponent regardless of the power of n chosen. The prepotential dependency of potassium current kinetics is inconsistent with the Hodgkin-Huxley axon model where the conductance parameters are assumed to be in either one of two possible states, and where the rate of transfer from one state to the other follows first order kinetics. In contrast the described kinetics may be consistent with complex multistate potassium "channel" models or membranes consisting of a number of types of channels.
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PMID:Effect of conditioning potential on potassium current kinetics in the frog node. 108 76

1. The nature and interactions of the membrane currents underlying induced pace-maker activity in frog atrial muscle have been investigated using a double sucrose gap technique. 2. The membrane current which controls the speed of the atrial pacemaker depolarization (the pace-maker current, ip), is shown to be an outward current activated within the plateau potential range of a normal action potential. The subsequent deactivation of ip at more negative potentials unmasks the depolarizing action of time-independent inward membrane currents so that a pace-maker potential can result. 3. The deactivation of ip over a limited potential range (between about -30 and -60 mV) can be reliably recorded by switching on the voltage clamp during an induced pace-maker depolarization. 4. Investigation of the time and voltage-dependent behaviour of ip over a much wider potential range is less straightforward. How ip can be separated from other components of outward current present in the decay tails following square voltage clamp depolarizations is described. 5. The majority of such current decay tails contain three components of outward current. It appears that two of these components, one of which is ip, are true Hodgkin-Huxley conductance systems chiefly carrying potassium ions. 6. The nature of the third current, which decays very slowly at moderate membrane potentials (about -40 mV), is discussed and reasons are briefly given for considering it to result from the accumulation of potassium ions in extracellular spaces. Preliminary evidence that potassium depletion occurs at potentials negative to the resting potential of the trabeculum is also presented. 7. Because of the obvious complexities involved, a quantitative analysis of the atrial outward currents is not attempted here but forms the subject of a following paper (Brown, Clark & Noble, 1976a).
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PMID:Identification of the pace-maker current in frog atrium. 108 55

To describe the kinetics of potassium permeability (conductance) changes in the squid giant axon membrane the Hodgkin--Huxley formulation uses a single first-order in time variable n with forward and backward rate constants, respectively alpha-n and beta-n, potential-dependent but time-independent. It has been shown by Frankenhaeuser that in the potassium-carrying system of the myelinated nerve fiber membrane of Xenopus laevis the rate constant beta-n is dependent on the duration of previous depolarization, i. e. the beta-n of this membrane is time-dependent. Started from the FitzHugh--Cole--Moore translation principle for potassium current experimental data of Frankenhaeuser have been analysed to show that the rate constant alpha-n in the X. laevis nerve fiber membrane is also time-dependent. To keep the conventional Hodgkin--Huxley formulation valid in case of the potassium-carrying system of the X. laevis nodal membrane involvement of an additional first--order in time component (n-II) has been postulated, which is compatible with Frankenhaeuser's experimental results. This component n-II appears to be identical to the n-II-component in the potassium-carrying system of the Rana ridibunda nerve fiber membrane. Both are rather slow and activated within the potential range more negative than the basic n-I-component (corresponding to Frankenhaeuser's variable n). The component n-I seems to be identical to the n-component of many other excitable membranes with fast action potentials. The existence of the third, very slow nIII-component is also possible. The independent components in question are believed to be associated with different independent potassium channels within the same membrane. It is likely that the existence of several independent components is a general feature of the potassium-carrying mechanism in the excitable membranes essential for a particular type of electrogenesis.
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PMID:[Time dependence of the reaction rate constant of potassium permeability of Ranvier's node membrane]. 111 3

Hodgkin and Huxley equations were modified to include the properties of an external diffusion barrier separated from the axolemma by a thin periaxonal space in which potassium ions accumulate as a function of membrane activity. Further modifications in the equations took into account new values for gK and new functions for alphan, betan, alphah, and betah derived from voltage clamp experiments on Loligo pealei giant axons. Equations were solved on a PDP-11 computer using the Gear predictor-corrector numerical method. In comparison with the original Hodgkin and Huxley equations, the modified equations for membrane potentials gave: 1) more accurate representations of the falling and undershoot phases of the membrane action potential, 2) more accurate representation of thresholds and latencies, 3) increases in the periaxonal space potassium ion concentration, Ks, of about 1 mM/impulse, 4) proper predictions of the time course and magnitude of either undershoot decline or periaxonal potassium ion accumulation during trains of membrane action potentials elicited by repetitivie short duration stimuli, and5) a somewhat more accurate representation of adaptation (finite train and nonrepetitive responses) during long duration constant current stimulation.
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PMID:Solutions of the Hodgkin-Huxley equations modified for potassium accumulation in a periaxonal space. 112 87

Light scattering studies on the giant squid axon were done using the technique of optical mixing spectroscopy. This experimental approach is based on the use of laser light to detect the fluctuations of membrane macromolecules which are associated with conductance fluctuations. The light scattering spectra were similar to the Lorentzian-like behavior of conductance fluctuations, possibly reflecting an underlying conformational change in the specific membrane sites responsible for the potassium ion conductance. The amplitude of the spectra measured, increased when the membrane was depolarized and decreased on hyperpolarization. The spectra were fit to the sum of two terms, a (1/f component and a simple Lorentzian term. Spectra from deteriorating axons did not show sensitivity to membrane potential changes. It is shown theoretically that fluctuations due to the voltage-dependent variable, n, of the Hodgkin-Huxley formalism are identical to the voltage fluctuations. The derived power spectrum is that of a second order system, capable of showing resonance peaking only if the voltage dependence of the potassium rate of constants is included in the analysis. The lack of resonance peaking in the observed light scattering spectra, indicates that the data are best described by a damped second order system.
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PMID:Light scattering spectroscopy of the squid axon membrane. 112 36


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