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

Activation of potassium conductance in squid axons with membrane depolarization is delayed by conditioning hyperpolarization of the membrane potential. The delayed kinetics superpose with the control kinetics almost, but not quite, exactly following time translation, as demonstrated previously in perfused axons by Clay and Shlesinger (1982). Similar results were obtained in this study from nonperfused axons. The lack of complete superposition argues against the Hodgkin and Huxley (1952) model of potassium conductance. The addition of a single kinetic state to their model, accessible only by membrane hyperpolarization, is sufficient to describe this effect (Young and Moore, 1981).
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PMID:Conditioning hyperpolarization delays in squid axon potassium channels. 242 15

Action potentials, macroscopic ionic currents and single channel currents were recorded from growth cones of Aplysia right upper quadrant (r.u.q.) cells in culture, using the patch-clamp technique. Recordings were obtained from both intact growth cones and from growth cones that had been mechanically isolated from the rest of the neurone. In current-clamp mode, greater than half of the isolated growth cones display an all-or-none action potential when depolarized above 0 mV with outward current pulses. The remaining growth cones display only a graded depolarization that is unaffected by tetrodotoxin (TTX). In whole-cell voltage clamp almost all isolated growth cones display a rapidly activating and inactivating inward current followed by a delayed outward current in response to depolarizations positive to -20 mV. The rapid inward current reverses direction at around +70 to +80 mV and is completely suppressed by 100 microM-TTX, which suggests that this current is carried by the fast Hodgkin-Huxley sodium current channels. The delayed outward current appears to result from the activation of both the delayed rectifier potassium current, IK, and the calcium-activated potassium current, IC. The growth cones do not display any prominent early transient outward current, IA. The sodium current, INA, was studied in isolation by substituting caesium for potassium ions in the pipette solution. INa is half-inactivated at a holding potential of -36 mV, reaches half-maximal activation with a depolarization to 0 mV, and has a mean peak current density of 13 microA/cm2. The time course of inactivation is well described by a single exponential (tau = 3 ms at 0 mV). In cell-attached patches, a rapidly activating and inactivating inward current channel was recorded with an average unit conductance of 6.9 pS. The activation and inactivation parameters of the ensemble averaged current closely match the measured values from the macroscopic sodium current. At very positive potentials we recorded a voltage-dependent outward current channel with a conductance of around 35 pS. No significant inward calcium current was observed in whole-cell measurements and few single calcium channel currents were measured in cell-attached patches, suggesting a sparse distribution of calcium channels in the r.u.q. growth cones.
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PMID:Action potentials, macroscopic and single channel currents recorded from growth cones of Aplysia neurones in culture. 242 3

The development of the intracellular perfusion technique made isolated nerve cells an extremely convenient object for the detailed study of calcium channels, which allow the corresponding ions to enter the cell through the surface membrane during excitation. A wide range of investigations conducted in this object has shown that calcium channels, allowing the passage of bivalent cations in the order of preference Ba greater than Sr greater than Ca greater than Mg, bind these ions with the aid of a binding group located inside the channel. Other bivalent cations (Co, Ni, Mn, Cd), which bind too strongly with this group, become competitive channel blockers. In the absence of bivalent cations in the extracellular medium the calcium channels lose their selectivity and begin to transmit monovalent cations effectively; the reason for this transformation is detachment of the bound calcium ions from a special regulating group at the mouth of the calcium channels. Calcium channels can exist in two functional states: conducting and nonconducting. The transition between these states is accompanied by movement of charges inside the membrane ("gating currents"). The statistical kinetics of this transition, like the kinetics of gating currents, can be described by a modified Hodgkin-Huxley equation, with an activation variable raised to the power of 2. During long-term membrane depolarization the calcium channels pass into an inactivated state, which is connected with the recurrent blocking action of calcium ions, entering the cell, on the channels. Meanwhile, for some types of calcium channels, potential-dependent activation analogous to that in sodium or potassium channels is observed.
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PMID:Calcium channels in the cell membrane. 243 85

(1) The effects of benzocaine on the ionic currents in the voltage-clamped squid giant axon have been examined under various conditions; intact axons, axons internally perfused with CsF and axons dialysed with tetraethylammonium ions were used. (2) Both the steady state outward (potassium) current and the early transient (sodium) current were reduced by ca. 50% by benzocaine (1 mM). (3) Plots of the changes produced by benzocaine (1 mM) in the Hodgkin-Huxley parameters for the steady state activation (m infinity), the steady state inactivation (h infinity) and the time constants (tau m and tau h) for activation and inactivation of the sodium current are shown. The m infinity and h infinity curves are shifted in positive and negative directions respectively on the voltage axis. The time constants are not greatly affected. (4) In axons in which the sodium current inactivation had been largely removed by treatment with chloramine T, the sodium current was still reduced by ca. 50% by 1 mM benzocaine and the positive shift in activation remained unchanged. (5) The dependence on benzocaine concentration (for less than or equal to 2 mM) of the peak sodium current reduction and the shift in steady state inactivation have been determined. (6) It is concluded that in the squid axon the effects on inactivation are not the main reason for the reduction of the sodium current by benzocaine and that, in common with many other neutral anaesthetics, there are at least two sites at which benzocaine acts.
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PMID:The mechanisms of sodium current inhibition by benzocaine in the squid giant axon. 244 18

The effects of fourteen halogenated ethers on the sodium and potassium currents of voltage-clamped squid giant axons have been examined. Effects under open-circuit were also studied. In voltage-clamped axons, the ethers tended to reduce potassium currents at least as much, if not more, than sodium currents. This finding distinguishes the halogenated ethers from many other general anaesthetics. Certain, but not all, halogenated ethers induced a pronounced maximum in potassium current traces as a function of time. This property can be formally described if an inactivation term is added to the Hodgkin-Huxley equation for potassium currents. Large shifts in the sodium-current inactivation parameter h infinity were produced in some instances. Two fully halogenated methyl ethyl ethers, known to produce convulsions in mice, depressed both sodium and potassium currents, but with a very slow time course of action. The electrophysiological effects of the halogenated ethers investigated appear to depend on the position and number of hydrogen bonds that can be formed.
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PMID:The actions of halogenated ethers on the ionic currents of the squid giant axon. 244 63

1 The actions of the class I anti-arrythmic agent, disopyramide, on the ionic currents of the voltage-clamped squid axon have been investigated, by use of both extra-axonal and intra-axonal routes of application. 2 Extra-axonal application of 0.1 mM disopyramide produced no significant effects on the membrane currents. External disopyramide at 1.0 mM caused small, poorly reversible inhibition of both sodium and potassium currents. This block was use-dependent and was enhanced by use of test stimuli to more positive membrane potentials. 3 Intra-axonal application of 0.1 mM disopyramide caused a 40% reduction in the first-pulse sodium current (tonic block) and an additional use-dependent block. Analysis of first-pulse currents in terms of the Hodgkin-Huxley formalism indicated that the block resulted mainly from a reduction in the maximum available sodium conductance (gNa); there were no effects on the voltage dependence of the steady-state activation and inactivation parameters, m infinity and h infinity. 4 The use-dependent actions of disopyramide were investigated with a double voltage-clamp pulse protocol. The significant use-dependent effects of the drug were a further reduction in gNa and an increase in the time constant of inactivation (tau h). 5 Disopyramide appears to enter a blocking site in the sodium channel which is only readily accessible from the axoplasmic phase. Partition to the site depends on membrane voltage and on the state of the channel gates. Disopyramide binds at a significant rate to both open and inactivated forms of the sodium channel.
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PMID:The effects of external and internal application of disopyramide on the ionic currents of the squid giant axon. 244 1

Since the work of A. L. Hodgkin and A. F. Huxley (1952. J. Physiol. [Lond.].117:500-544) the squid giant axon has been considered the classical preparation for the study of voltage-dependent sodium and potassium channels. In this preparation much data have been gathered on macroscopic and gating currents but no single sodium channel data have been available. This paper reports patch clamp recording of single sodium channel events from the cut-open squid axon. It is shown that the single channel conductance in the absence of external divalent ions is approximately 14 pS, similar to sodium channels recorded from other preparations, and that their kinetic properties are consistent with previous results on gating and macroscopic currents obtained from the perfused squid axon preparation.
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PMID:Single sodium channels from the squid giant axon. 244 71

1. Neurones were isolated from the CA1 region of the guinea-pig hippocampus and subjected to the whole-cell mode of voltage clamping, to determine the kinetics of voltage-gated Ca2+ channel activation. 2. Isolated neurones had an abbreviated morphology, having lost most of the distal dendritic tree during the isolation procedure. The electrical compactness of the cells facilitates voltage clamp analysis. 3. Block of sodium and potassium currents revealed a persistent current activated on depolarization above -40 mV, which inactivated slowly when the intracellular medium contained EGTA. The current was blocked by Co2+ and Cd2+, augmented by increases in Ca2+ and could be carried by Ba2+, suggesting that the current is borne by Ca2+. 4. Steady-state activation of the Ca2+ current was found to be well described by the Boltzman equation raised to the second power. 5. The open channel's current-voltage (I-V) relationship rectified in the inward direction and was consistent with the constant-field equation. 6. The kinetics of Ca2+ current onset followed m2 kinetics throughout the range of its activation. Tail current kinetics were in accord with this model. A detailed Hodgkin-Huxley model was derived, defining the activation of this current. 7. The kinetics of the currents observed in this regionally and morphologically defined class of neurones were consistent with the existence of a single kinetic class of channels.
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PMID:Calcium current activation kinetics in isolated pyramidal neurones of the Ca1 region of the mature guinea-pig hippocampus. 245 32

The non-selective channel for monovalent cations of cultured brown adipocytes was studied concerning its permeability to alkali metal ions, NH4+, Tris+, Ca2+, and Ba2+. Experiments were done by means of the patch clamp technique using inside-out patches. With symmetrically increasing sodium concentrations the ion fluxes saturated. They are described by a dissociation constant (KNa) of 155 mmol/l and a maximum single channel conductance of 50 pS. Permeabilities were determined in relation to those for sodium yielding values of 0.80 for potassium and 1.55 for ammonium. The complete permeability sequence for ammonium and the alkali metals is: NH4+ greater than Na+ greater than Li+ greater than K+ greater than or equal to Rb+ congruent to Cs+ . Ca2+ and Ba2+ as well as the buffer ion Tris+ are not able to pass the channel measurably. It is shown that the conductance behaviour of the non-selective channel is not sufficiently described by the Goldman-Hodgkin-Katz theory. Deviations from independence are saturation with increased activity of the permeant ion and non-linear current voltage relations in symmetrical solutions. A simple two barrier model with one binding site in the center of the electric field is shown to be more appropriate.
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PMID:Permeability of the non-selective channel in brown adipocytes to small cations. 247 15

The calcium current of bullfrog sympathetic neurons activates and deactivates rapidly (tau less than 3 ms). For brief depolarizations, the current can be fit reasonably well by a Hodgkin-Huxley-type model with a single gating particle of charge +3. With 2 mM Ca2+ as the charge carrier, half-maximal activation occurs at approximately -5 mV, near the voltage where activation and deactivation are slowest. When extracellular divalent ion concentrations are reduced, monovalent ions (e.g., Na+ and methylammonium) produce kinetically similar inward currents. Current carried by Ba2+ is blocked by Cd2+ at micromolar concentrations, and by 100 nM omega-conotoxin. Commercially available saxitoxin blocks the current, but different batches have quantitatively different potency. The dihydropyridine agonist Bay K 8644 induces a slight shift in activation kinetics to more negative voltages, with little effect on the peak current. Nifedipine at least partially reverses the effect of Bay K 8644, but has little effect on its own. Muscarinic agonists and other ligands that inhibit the M-type potassium current of frog sympathetic neurons have weak inhibitory effects on the calcium current as well. One interpretation of these results is that the N-type calcium current predominates in these cells, with a minor contribution of L-type current.
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PMID:Calcium currents in bullfrog sympathetic neurons. I. Activation kinetics and pharmacology. 247 59


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