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)

The Hodgkin-Huxley kinetic parameters, alpha h and beta h, which govern the rate of recovery from and development of sodium channel inactivation, respectively, have been measured as a function of membrane potential and external pH using a three-pulse protocol. alpha h but not beta h is substantially accelerated by reducing external pH from 7.4 to 6.4. The alpha h vs. voltage curve appears to be selectively shifted in the depolarizing direction by approximately 12 mV for this pH change, giving an apparent, h infinity curve shift of approximately 6 mV in the same direction (less inactivation).
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PMID:Extracellular pH selectively modulates recovery from sodium inactivation in frog myelinated nerve. 4 11

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

The theoretical power density spectrum S(f) of ion current noise is calculated from several models of the sodium channel gating mechanism in nerve membrane. Sodium ion noise experimental data from the frog node of Ranvier [Conti, F., et al. (1976), J. Physiol. (London) 262:699] is used as a test of the theoretical results. The motivation for recent modeling has been evidence for a coupling between sodium activation and inactivation from voltage clamp data. The two processes are independent of one another in the Hodgkin and Huxley (HH) model [Hodgkin A.L., Huxley, A.F. (1952), J. Physiol. (London) 117:500]. The noise data is consistent with HH, as noted by Conti et al. (1976). The theoretical results given here appear to indicate that only one case of coupling models is also consistent with the noise data.
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PMID:Comparison of ion current noise predicted from different models of the sodium channel gating mechanism in nerve membrane. 35 12

An analysis of ionic channel conductance is presented in terms of dipole cooperative model. The dependence of conductance on displaced charge is found to be an S-shaped function. Basing on this function and kinetics of gating currents, the kinetic curves for the conductance are calculated. These curves are compared with Hodgkin--Huxley results on sodium channel. A good agreement may be observed for the case of positive jumps of the potential. Less accurate coincidence takes place for negative jumps of the potential.
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PMID:[Dipole cooperative model of ion channels of excitable biomembranes. Conductance of ion channels]. 67 72

Yohimbine, an indolealkylamine alkaloid, reduces the amplitude of the sodium current in the squid giant axon. For doses that reduce sodium current amplitude by up to 50%, there is no significant change in the kinetics or in any of the voltage-dependent parameters associated with sodium channels. The effective equilibrium constant for yohimbine binding to the sodium channel is 3 x 10(-4) M. Repetitive depolarizing pulses increase the inhibition of squid axon sodium current by yohimbine. This use-dependent inhibition is enhanced by increasing the concentration of yohimbine, by increasing the frequency of pulsing, and by increasing the magnitude or the duration of depolarization. It is reduced by hyperpolarizing prepulses. This behavior can be explained by a model wherein yohimbine binds more readily to open sodium channels than to closed sodium channels and wherein the Hodgkin-Huxley kinetic parameters are modified by the binding of the drug. This type of model may also explain the tonic and use-dependent inhibition previously described by others for local anesthetics.
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PMID:Effects of yohimbine on squid axons. 72 22

The behavior under voltage clamp conditions of a coupled kinetic scheme for the sodium channel is examined. The scheme is given diagrammatically by: Numerical simulations are presented which show that this model fits the voltage clamp data which are well described by the Hodgkin-Huxley equations, but also gives the sorts of behavior anomalous to the Hodgkin-Huxley model which have been seen experimentally. Further, straightforward changes in parameter values are shown to be capable of mimicking the ways in which some axonal preparations differ from others. Detailed, but admittedly heuristic, arguments are presented for the propositions that: 1) the model is minimal; i.e. no simpler kinetic model will fit the array of data simulated, and: 2) the transient excited state is necessary; i.e. no model of comparable simplicity with pure voltage dependent kinetics will fit the array of data simulated.
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PMID:A fully coupled transient excited state model for the sodium channel. I. Conductance in the voltage clamped case. 73 Nov 34

The axon membrane is simulated by standard Hodgkin-Huxley leakage and potassium channels plus a coupled transient excited state kinetic scheme for the sodium channel. This scheme for the sodium channel is as proposed previously by the author. Simulations are presented showing the form of the action potential, threshold behavior, accommodation, and repetitive firing. It is seen that the form of the individual action potential, its all-or-none nature, and its refractory period are well simulated by this model, as they are by the standard Hodgkin-Huxley model. However, the model differs markedly from the Hodgkin-Huxley model with respect to repetitive firing and accommodation to stimulating currents of slowly rising intensity, in ways that are shown to be related to those features of the sodium inactivation which are anomalous to the H-H model. The tendency for repetitive firing is highly dependent on that parameter which primarily determines the existence of the inactivation shift in voltage clamp experiments, in such a way that the more pronounced the inactivation shift, the less the tendency for repetitive firing. The tendency for accommodation is highly dependent on that parameter which primarily determines the 'tauc-tauh' separation, in such a way that the greater the separation the greater the tendency for the membrane to accommodate without firing action potentials to a slowly rising current.
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PMID:A fully coupled transient excited state model for the sodium channel. II. Implications for action potential generation, threshold, repetitive firing, and accommodation. 75 Jun 31

Studies on the kinetics of activation and inactivation of the sodium channels of the squid giant axon, on the sodium gating current, and on the properties of the non-inactivating steady-state current, are briefly reviewed. Taken in conjunction with recent evidence on the structure of voltage-gated ion channels, they have led to the development of a series-parallel model of the sodium channel that can be regarded as a modernized version of the Hodgkin-Huxley model, with some novel features. It is suggested that activation results from conformational changes brought about by the four S4 voltage sensors operating in parallel, each of which makes two discrete steps to reach the fully activated state of the channel. There follows a voltage-independent hydration step, and the channel is ready to open. Inactivation is a potential-dependent process involving a third transition of voltage sensor S4d alone, which, rather than bringing a ball and chain blocking group into position to close the channels, serves to switch the system so that it passes from an initial activated mode, in which there is a high probability of arriving at an open state with a brief latency, to a second steady-state mode, in which the probability of opening is very much lower.
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PMID:A new look at the mechanism of activation and inactivation of voltage-gated ion channels. 127 3

Currents through DPI 201-106 modified single sodium channels have been measured in cell-free inside-out patches from guinea-pig ventricular myocytes. Single-channel conductance and reversal potential of the sodium channel have been calculated at different intracellular sodium concentrations [( Na+]i) from microscopic I-V curves, which were obtained by application of linear voltage ramps. The relation between the reversal potential and [Na+]i could be fitted with a modified Goldman-Hodgkin-Katz equation with a relative permeability for K+ over Na+ ions of 0.054. The zero-current conductance of the Na channel as a function of [Na+]i shows a plateau value at low Na concentrations, and increases in a sigmoidal manner at higher concentrations. It is concluded that the Na channel can carry outward currents and that its conductance depends on [Na+]i.
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PMID:The conductance of single cardiac sodium channels from guinea pig depends on the intracellular sodium concentration. 165 33

The sodium (Na) channel is the fundamental unit of excitability in heart muscle. This channel has been very difficult to study in detail, because the major experimental tool, the voltage clamp, has been difficult to use in multicellular tissue. In the absence of more direct studies in the heart, it has been assumed that the sodium channel in the heart was the same as that in nerve tissue, where it could be studied quantitatively. However, the sodium channel is not likely to be the same as in nerve, because it responds differently to local anesthetics and to other drugs such as tetrodotoxin. It is essential to learn the details of the cardiac sodium channel, because it is the membrane process that underlies many lethal cardiac arrhythmias, and it is the molecular site of action of the most effective antiarrhythmic drugs. Single cardiac Purkinje cells were dialyzed at room temperature through a large bore pipette, and their Na+ currents were studied under voltage clamp control. The peak currents were 0.5 to 1.0 mA/cm2, assuming a 1 mu farad/cm2 membrane. Peak currents near 0 mV were achieved in less than 1 ms. The decay of the Na+ current did not correspond to a single exponential process. This result and the observation that recovery from inactivation occurred with a latency are inconsistent with the original Hodgkin-Huxley model, but they qualitatively fit a model with two sequential inactivated states or a model with two kinetically different types of Na+ channels. The steady state inactivation curve shifted in the negative direction after initiation of intracellular dialysis, stabilizing with a half-availability voltage of -115 mV.
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PMID:Sodium currents in single cardiac Purkinje cells. 242 74


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