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)

1. The effects of 'clinical' concentrations of some general anaesthetics on the minimum stimulus required to produce an action potential in the squid giant axon have been examined as a function of time from exposure to the anaesthetic. The resting potential in these experiments was also monitored. 2. The minimum stimulus varied with time in different ways for different anaesthetics. For chloroform, diethyl ether, n-pentanol, halothane and cyclopropane the stimulus initially declined, reached a minimum after about 3 min and then recovered to near-normal values at 10-15 min. For n-pentane, cyclopentane and, to a lesser extent methoxyflurane, the stimulus often declined to such low values that the axon exhibited spontaneous action potentials which persisted until the anaesthetic was removed. For one substance, the experimental local anaesthetic diheptanoyl phosphatidylcholine, the stimulus increased considerably over the 10-15 min required to reach the steady state. In all instances the axons reverted to normal behaviour after removal of the anaesthetic although the time course by which they did so was more variable than for the initial exposure. 3. For all anaesthetics the resting potential changed in the positive direction monotonically by ca. 1-5 mV and reached a steady state in approximately 3 min. On removal of the anaesthetic the resting potential returned to normal, also monotonically. 4. The voltage-gated Na+ and K+ currents were significantly affected even at the low anaesthetic concentrations used. Estimates of the changes in the Hodgkin-Huxley parameters were obtained partly by direct experiment and partly from results previously obtained for higher anaesthetic concentrations. 5. The time dependencies of the minimum stimuli have been accounted for semi-quantitatively in terms of the resting potential changes and the voltage shifts in the Na+ current steady-state activation, and the time dependencies respectively of these two parameters. 6. Quantitative calculations of the resting potential changes for comparison with experiment have been made based on the changes in K+ conductance determined in the preceding paper (Haydon, Requena & Simon, 1988) and changes in the Hodgkin-Huxley parameters of the Na+ and delayed-rectifier K+ currents. 7. Calculations of the minimum stimulus in the steady state have been made from the experimental resting potential changes and from the anaesthetic-affected Hodgkin-Huxley parameters. Good agreement with the experimental stimuli was found, especially in the prediction of high and low values.
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PMID:Excitation of the squid giant axon by general anaesthetics. 323 44

A number of small organic molecules with general anaesthetic action have been examined for their effects on the voltage-dependent potassium current of the squid giant axon. They include representatives of the three classes of anaesthetics examined in previous studies on the sodium current (Haydon & Urban, 1983a, b, c), i.e. the non-polar molecules n-pentane, cyclopentane and CCl4, several n-alkanols and the inhalation anaesthetics chloroform, halothane, diethyl ether and methoxyflurane. Potassium currents under voltage clamp were recorded in intact and in intracellularly perfused axons before, during and after exposure to the test substances, and the records were fitted with equations similar to those proposed by Hodgkin & Huxley (1952). Shifts in the curves of the steady-state activation against membrane potential and reductions in the potassium conductance at 60 or 70 mV membrane potential have been tabulated. On the same intact axons, all the anaesthetics with the exception of methoxyflurane reduced potassium currents less than sodium currents by about a factor of two or more. For the n-alkanols, butanol to decanol, the concentrations required to reduce the potassium current at 60 mV membrane potential by 50% were determined. For n-butanol to n-heptanol, the standard free energy per CH2 for adsorption to the site of action was estimated to be -2.91 kJ mol-1 as compared with -3.04 kJ mol-1 for reduction of the sodium current. The magnitude of the free energy decreased for alkanols with longer chain lengths. At anaesthetic concentrations that reduce the sodium current by 50%, the hydrophobic substances n-pentane and cyclopentane reduced the maximal sodium conductance, gNa, and the potassium conductance at 70 mV, gK70, equally by about a third, while the n-alkanols reduced both parameters by less than 10%. By contrast, diethyl ether and methoxyflurane were more effective in reducing the maximal potassium conductance. All of the test substances examined, except n-pentane and n-hexane, shifted the voltage dependence of the potassium steady-state activation in the depolarizing direction. A broad qualitative correlation was found between the shifts in the activation curves for sodium and potassium currents but, quantitatively, the agreement between the two shifts was poor. In n-decanol and methoxyflurane solutions, the voltage-clamped potassium currents exhibited pronounced inactivation-like behaviour. These currents can be fitted by the Hodgkin-Huxley formalism if an inactivation term analogous to the sodium current inactivation is added.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The actions of some general anaesthetics on the potassium current of the squid giant axon. 374 76

The effects of the n-alkanes propane to hexane, cyclopropane, cyclopentane and cyclohexane and carbon tetrachloride on the ionic currents and electrical capacity of the squid giant axon membrane have been examined. Both the peak inward and steady-state outward currents were reduced reversibly by each substance, though propane at 1 atm had very little effect. The membrane capacity at 100 kHz was reduced by all substances except propane at 1 atm. Na currents were recorded in intracellularly perfused axons before and during exposure to the hydrocarbons and the records were fitted with equations similar to those proposed by Hodgkin & Huxley (1952). Shifts in the curves of the steady-state activation and inactivation parameters (m infinity and h infinity) against membrane potential, changes in the peak heights of the activation and inactivation time constants (tau m and tau h) and reductions in the maximum Na conductance (gNa) have been tabulated. The effects of the various hydrocarbons and carbon tetrachloride on the parameters of the Hodgkin-Huxley equations suggest that the suppression of the Na current by these substances originates from several different phenomena. The underlying physico-chemical events are considered in the light of the observed capacity changes and of information on artificial pore-containing membranes.
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PMID:The action of hydrocarbons and carbon tetrachloride on the sodium current of the squid giant axon. 687 65