n-Alkanols potentiate sodium channel inactivation in squid giant axons

Oxford, Gerry S.; Swenson, Randolphe P.

doi:10.1016/s0006-3495(79)85273-x

Cited by 48 publications

(22 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is unlikely, therefore, that the alcohols would suppress excitability in a nerve in exactly the same way as do the hydrocarbons. From the work of Armstrong & Binstock (1964), Moore, Ulbricht & Takata (1964), Oxford & Swenson (1979) and others it is already clear that differences exist. The most obvious of these is in the steady-state inactivation curve where hydrocarbons produce large hyperpolarizing shifts while the alcohols have little effect.…”

Section: Dahaydonandb W Urban Introductionmentioning

confidence: 99%

“…The h. curves have not been shown for membrane potentials less negative than -25 mV but it was noted that in this potential range the residual Na current was strongly suppressed by all of the above-mentioned substances. Oxford & Swenson (1979) have drawn attention to this effect for n-octanol and n-decanol. The hydrocarbons produce large negative shifts in the hgo, curve and also reduce the slope of the curve at its mid-point.…”

mentioning

confidence: 99%

See 1 more Smart Citation

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

Haydon¹,

Urban²

1983

The Journal of Physiology

103

View full text Add to dashboard Cite

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.

show abstract

Section: Dahaydonandb W Urban Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

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

Haydon¹,

Urban²

1983

The Journal of Physiology

103

View full text Add to dashboard Cite

show abstract

“…A variety of mechanisms could underlie the overall increase in threshold found with most of the agents tested, the most obvious being reduced maximum gNa, which has been observed with alkanols and volatile anaesthetics in both invertebrate and vertebrate axons under voltage-clamp conditions (e.g., Kendig et al, 1979;Oxford & Swenson, 1979;Haydon & Urban, 1983a,b). By and large our data for the potency of alkanols on the mouse nerve terminal are consistent with those on squid axon (Haydon & Urban, 1983a rather small reduction in peak sodium current in squid axon with concentrations of methoxyflurane and halothane six and ten times larger than used here, indicating either that the mouse nerve terminal is more sensitive, or that other mechanisms underlie the change in excitability that we observed with these agents.…”

Section: Discussionmentioning

confidence: 99%

Modification of motor nerve terminal excitability by alkanols and volatile anaesthetics

Quastel

Saint

1986

British J Pharmacology

View full text Add to dashboard Cite

A method of local polarization‐excitation was used to study changes in motor nerve terminal excitability produced by n‐alkanols and volatile anaesthetics in mouse diaphragm preparations. Ethanol and propanol caused an exaggeration of ‘accommodation’, i.e., the increase in excitation threshold produced by a conditioning depolarization. Butanol, hexanol and octanol had mixed effects, producing a rise in the minimum threshold (threshold after removal of resting accommodation) in addition to an increase in accommodation. Volatile anaesthetics produced effects on excitability at concentrations comparable to minimum alveolar concentration. The action of enflurane was essentially only to increase accommodation while methoxyflurane produced an increase in threshold insensitive to conditioning polarization. Halothane and isoflurane produced intermediate effects. Accommodation curves were little affected by Ba2+ or 4‐aminopyridine and were consistent with accommodation being a reflection of inactivation of the Na+ current system. We conclude that volatile anaesthetics, at concentrations comparable to those producing anaesthesia, may substantially modify Na+ channel gating and inactivation.

show abstract

“…The first was to determine the effects of a homologous series of model anaesthetic compounds, the n-alkanols, on a channel which is primarily involved in regulating the threshold behaviour of a neurone. The intention was to complement the work of others who have been concerned with the actions of n-alkanols on voltage-gated sodium currents ('Na) (Armstrong & Binstock, 1964; Oxford & Swenson, 1979;Swenson & Narahashi, 1980;Haydon & Urban, 1983;Paternostre, Pichon & Dupeyrat, 1983; Hirche, 1985;Nelson & Makielski, 1991); delayed rectifier potassium currents (IK) (Pasternostre et al 1983;Haydon & Urban, 1986); calcium currents ('Ca) (Oyama, Akaike & Nishi, 1986) and resting potassium conductances ('Kr) . Treistman & Wilson (1987a, b) described the effects of three short-chain n-alkanols (ethanol, n-butanol and n-hexanol) on IA currents in Aplysia neurones.…”

Section: Introductionmentioning

confidence: 99%

Effects of n‐alkanols and a methyl ester on a transient potassium (IA) current in identified neurones from Helix aspersa.

Winpenny

Elliott

Harper

1992

The Journal of Physiology

View full text Add to dashboard Cite

SUMMARY1. A two-microelectrode voltage clamp was used to determine the effects of n-butanol, n-hexanol, n-octanol, n-decanol and methyl hexanoate on a transient potassium (IA) current in identified Helix aspersa neurones. Experiments were carried out at a temperature of 10-12 'C.2. Each n-alkanol reversibly reduced the amplitude of the IA current. Logarithmic dose-response curves for the current reduction by each homologue were sigmoidal and had slope factors of around four. The concentrations required to reduce the peak (with time) current at -30 mV by 50 % (ED50 ± fitted standard error) were: 57+5 mM (n-butanol); 2-0 + 0-1 mm (n-hexanol); 0-28 + 0-02 mm (n-octanol) and 0-016+ 0.001 mM (n-decanol). Methyl hexanoate also reduced the current amplitude, with an ED50 of 1-2 mm. The Helix IA current thus showed a similar sensitivity to nalkanols to that of squid and rat sodium currents but was rather more sensitive than the squid delayed rectifier potassium current.3. The n-alkanol ED50 concentrations were used to calculate a standard free energy per methylene group for adsorption to a site of action in the cell of -3-1 + 0-2 kJ/mol. This suggested a hydrophobic site or sites of action. The regularity of the change in free energy with chain length was maintained up to, and including, n-decanol. This implied that the site(s) could accommodate a ten-carbon chain as readily as an eight-carbon chain.4. The voltage dependencies ofIA current activation and steady-state inactivation were not consistently altered by treatment with n-alkanols at concentrations around or above their current suppression ED50 concentrations.5. The kinetics of current activation and inactivation were affected, particularly by lower chain length compounds. At 60 mM n-butanol reduced the time constant for development of inactivation of open channels (Tb) by 56 %, while 0-016 mM n-decanol produced only a 13% reduction. n-Butanol (60 mM) also caused a substantial (76%) reduction in the time constant for development of inactivation in channels which were presumed to be closed. The effects of n-alkanols on the current time-to-peak (tj) were complex, showing both increases and decreases, but these actions also declined with chain length. J. P. WINPENNY, J. R. ELLIOTT AND A. A. HARPER conductances. However, even quite superficial analyses of the mechanisms underlying the inhibition of such conductances have revealed a substantial specificity of action of these structurally simple compounds. The evidence for this specificity and the subsequent implications for more general theories of channel perturbation will be discussed.

show abstract

n-Alkanols potentiate sodium channel inactivation in squid giant axons

Cited by 48 publications

References 16 publications

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

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

Modification of motor nerve terminal excitability by alkanols and volatile anaesthetics

Effects of n‐alkanols and a methyl ester on a transient potassium (IA) current in identified neurones from Helix aspersa.

Contact Info

Product

Resources

About