Some effects of n‐pentane on the sodium and potassium currents of the squid giant axon.

Self Cite

104

SUMMARY1. The effects of diethyl ether, methoxyflurane, halothane, dichloromethane and chloroform on the ionic currents and electrical capacity of the squid giant axon have been examined.2. The peak inward current in voltage-clamped axons was reduced reversibly by each substance. Sodium currents under voltage clamp were recorded in intracellularly perfused axons before, during, and sometimes after exposure to the test substances, and the records were fitted with equations similar to those proposed by Hodgkin & Huxley (1952).3. Shifts in the dependence of the steady-state activation and inactivation parameters (moo,, and h.o) on membrane potential, reductions in the peak heights of the activation and inactivation time constants (Tm and Th) and decreases in the maximum Na conductance (kNa) have been tabulated.4. For each of the anaesthetics the steady-state inactivation curve was shifted in the hyperpolarizing direction though less markedly than for the hydrocarbons. The steady-state activation curve was in each instance shifted in the depolarizing direction, as for the alcohols and other surface active substances. In common with both the hydrocarbons and the surface active substances the peak time constants were invariably reduced.5. The membrane capacity at 100 kHz was affected significantly only by methoxyflurane, where decreases of ca. 9 % were observed for 3 mm solutions.6. The extent to which the results can be accounted for in terms of the perturbation of membrane lipid has been discussed.

Section: The Hodgkin-huxley Parametersmentioning

confidence: 62%

“…The voltage clamp and data acquisition procedures were as in Kimura & Meves (1979) and the analysis of the sodium currents was as described by Haydon & Kimura (1981). Compensation for the series resistance was applied in all experiments.…”

Section: Methodsmentioning

confidence: 99%

The effects of some inhalation anaesthetics on the sodium current of the squid giant axon.

Haydon¹,

Urban²

1983

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104

“…The effects of non-polar lipophilic substances, comprising a range of straight chain and cyclic hydrocarbons and carbon tetrachloride, on the Na current of the squid giant axon have been described in three earlier papers (Haydon, Requena & Urban, 1980;Haydon &Kimura, 1981 andHaydon &Urban, 1983). It has been shown that these substances affect several of the Hodgkin-Huxley parameters and that the way in which they do so is consistent with their adsorption into the interior of a lipophilic region so causing its expansion in a direction normal to the membrane surface.…”

Section: Dahaydonandb W Urban Introductionmentioning

confidence: 86%

The action of alcohols and other non‐ionic surface active substances on the sodium current of the squid giant axon.

Haydon¹,

Urban²

1983

Self Cite

103

SUMMARY1. The effects of several n-alkanols and n-alkyl oxyethylene alcohols, methyl octanoate, glycerol 1-monooctanoate and dioctanoyl phosphatidylcholine on the ionic currents and electrical capacity of the squid giant axon membrane have been examined.2. The peak inward current in voltage-clamped axons was reduced reversibly by each substance.3. For n-pentanol to n-decanol the concentrations required to suppress the peak inward current by 50 % were determined. From these data, it was estimated that the standard free energy per CH2 for adsorption to the site of action was -3 04 kJ mole-', as compared with -3-11 kJ mole-' for adsorption into phospholipid bilayers or an n-alkane/aqueous solution interface. 4. The membrane capacity at 100 kHz was not greatly affected by any of the test substances at concentrations which reduced the inward current by 50 %.5. Na currents under voltage clamp were recorded in intracellularly perfused axons before, during and sometimes after exposure to the test substances and the records were fitted with equations similar to those proposed by Hodgkin & Huxley (1952).6. Shifts in the curves of the steady-state activation and inactivation parameters (mo and h.o) against membrane potential, changes in the peak heights of the activation and inactivation time constants (Tm and Th) and reductions in the maximum Na conductance (gNa) have been tabulated.7. All of the test substances shifted the voltage dependence of the steady-state activation in the depolarizing direction and lowered the peak time constants for both activation and inactivation. The origins of these effects, and of the differences in the present results from those of the hydrocarbons (Haydon & Urban, 1983), have been discussed in terms of the physico-chemical properties of the two groups of substances and with reference to their effects on artificial membranes.

“…Of the other anaesthetics, mentioned at the outset, chloroform and carbon tetrachloride gave results more like those for the hydrocarbons, while the data for ethyl ether had many features in common with the alcohols. Halothane and methoxyflurane occupied central positions.It may be relevant that in their interactions with lipid bilayers, hydrocarbons and alcohols show similarities (membrane fluidity and tension increases) but also differences (hydrocarbons increase thickness whereas alcohols do not) (Colley & Metcalfe, 1972; Ebihara, Hall, MacDonald, McIntosh & Simon, 1979;Elliott & Haydon, 1979; Haydon & Kimura, 1981; and Hodgkin & Huxley (1952), has long been lacking. When the stochastic nature of the gating process is considered, however, it is found that a small change in membrane voltage can mobilize the large existing electrochemical potential difference across the membrane, and thus produce a much greater conductance change than is to be expected from earlier theories (Offner, 1980 In the present experiments, the output of a specially designed low noise voltageclamp amplifier was connected via a 1 Hz-3 KHz window to a low noise differential amplifier with a gain of 1000.…”

mentioning

confidence: 99%

“…It may be relevant that in their interactions with lipid bilayers, hydrocarbons and alcohols show similarities (membrane fluidity and tension increases) but also differences (hydrocarbons increase thickness whereas alcohols do not) (Colley & Metcalfe, 1972;Ebihara, Hall, MacDonald, McIntosh & Simon, 1979;Elliott & Haydon, 1979;Haydon & Kimura, 1981;and …”

mentioning

confidence: 99%

Communications

1981

PHYSIOLOGICAL SOCIETY, JUNE 1981 is brought into focus. With video-image analysis and stage-stepping motors under computer control it is possible to focus automatically. Coleman, Garvey, Young & Simon (1977) developed an auto-focus for Golgi material which selected the position of darkest image. However, we have found it more appropriate to use the position of maximum smoothed-edge contrast for less-densely or less-uniformly stained neurones, e.g. those injected with Procion Yellow or HRP. The auto-focus described here was designed to allow the operator to concentrate fully on the location and classification of structures in the (XY) image plane and on error correction. As a bonus, it was found to be faster and more reliable than manual focusing.The Magiscan (Joyce Loebl) was used to analyse the video image automatically and to control the microscope stage. A high-power ( x 50) objective was used to sharpen the focus plane. Each neuronal structure was traced in the XY plane with a sequence of point pairs, either by automatic edge-tracing or manually with a light pen. A four pixel (approximately 0 7 jsm) square was centred on each of these two reference points. Grey levels from the sixteen outermost points of each square were used to estimate smoothed-edge contrast; the degree of focus was defined as the sum of the two maximum values obtained when adding grey levels from each four successive points along the edges of the two squares and subtracting those from the next four points. The video image was analysed at sixty-four levels of grey. At this sensitivity the noise in our standard Bosch camera resulted in fluctuations in grey readings of up to + 2 levels. The resulting variability in Z estimates was reduced to within ± 1 ,um step by adding results from two (25 Hz) video scans and smoothing the degree-of-focus curve (adding results from each three successive focus positions). The stability and sensitivity of this final measure was such that a fast adaptive scanning procedure could be used, mimicking manual focusing; instead oftesting over a relatively wide fixed range, the upward and downward movements were each stopped as soon as the focus measure was less than 98 % ofits maximum value (usually within 3 ,um steps).Supported by the M.R.C. REFERENCE COLEMAN, P. D., GARVEY, C. F., YOUNG, J. H. & SIMON, W. (1977 The results for the different anaesthetics showed trends in which the hydrocarbons lay at one extreme and the alcohols at the other. At concentrations which suppressed the Na current (at the potential ofits peak under control conditions) by approximately 50 %, the hydrocarbons moved the mid-point of the steady state inactivation (hz) curve and the peak of the inactivation time constant (Th) by ca. 15 mV in the hyperpolarizing direction. n-Pentanol, n-octanol and n-C8H17(0. CH2CH2)30H, by contrast, produced shifts (in the same direction) of less than 1 to 2 mV. The effects of the hydrocarbons and alcohols on the mid-point of the steady state activation (moo) curve on the peak of the activation time ...