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Biomedical subjects

J R Elliott

Publications and source records attributed to J R Elliott.

At least 55 records · Page 3Linked to original sources
PubMed1985

Dual effects of internal n-alkyltrimethylammonium ions on the sodium current of the squid giant axon.

The actions of members of the homologous series of alkyl cations CH3 (CH2)n-1 N+ (CH3)3 (Cn TMA) on the sodium current in giant axons of Loligo forbesi have been investigated. The substances tested correspond to n = 6, 8, 10, 12, 14 and 16. These cations only produced significant sodium current suppression when applied inside the axon. Actions on first-pulse sodium currents and use-dependent effects were separately studied. The shorter members of the series (C6TMA and C8TMA) produced suppression of first-pulse sodium currents without causing significant use dependence. The first-pulse suppression arose partly from a positive shift along the voltage axis of the steady-state activation parameter (m infinity) and partly from a reduction in the maximum sodium conductance (gNa). C12TMA and C14TMA produced little first-pulse suppression but caused clear use dependence. C10TMA showed intermediate properties while C16TMA was inactive. The use-dependent actions have been quantitatively investigated using a double-pulse protocol. The results are consistent with a model in which the cations enter a blocking site on the ion-channel via the intra-axonal aqueous phase. The cations appear able to bind to inactivated sodium channels at significant rates. The possible molecular locations of the sites responsible for m infinity shifts and use dependence are discussed. It is argued that the existence of two separate sites may help to explain certain distinctions between the actions of neutral general anaesthetics and clinical local anaesthetics on the sodium channel.

Action Potentials↗
PubMed1984

The influence of n-alkanols on the capacity per unit area of planar lipid bilayers.

The electrical capacities per unit area of planar lipid bilayers formed from monoolein/n-hexadecane, monoolein/ squalane (or squalene) and monoolein/triolein have been measured in the presence of a range of n-alkanols. For monoolein/n-hexadecane bilayers, the effects of the n-alkanols are complicated but can be rationalized in terms of the likely changes in lipid chain order and the influence of the n-alkanol in the Plateau-Gibbs border. Monoolein/ squalane (or squalene) and monoolein/triolein bilayers exhibit behaviour quite different from the n-hexadecane membranes. For both the squalane and triolein bilayers the shorter chain alkanols increase the capacity per unit area while the longer homologues have little effect. These results help to account for the influence of the n-alkanols on gramicidin single-channel lifetimes.

Alcohols↗
PubMed1984

The asymmetrical effects of some ionized n-octyl derivatives on the sodium current of the giant axon of Loligo forbesi.

The effects of octyltrimethylammonium ions (OTMA+), octyl sulphate ions (OS-) and octanoic acid (OA) on the sodium current of the voltage-clamped squid giant axon have been investigated using intracellular and extracellular application of the test substances. OTMA+ applied externally at concentrations of 0.8-5.0 mM produces a small reversible increase in the peak inward sodium current in both intact and CsF-perfused axons. Intracellular application of OTMA+ at 0.8 mM to CsF-perfused axons causes a reversible 50% suppression of peak inward sodium current. The inhibition of peak inward current by internal OTMA+ arises largely from a shift of the steady-state activation parameter (m infinity) in the depolarizing direction along the voltage axis. There is little use dependence of the current suppression by OTMA+ OA applied either internally or externally is more effective at suppressing peak inward sodium current at pH 6.0 than at pH 7.4. At pH 6.0 external application of 5 mM-OA to perfused axons causes approximately 60% suppression. This is associated with a depolarizing shift of m infinity of about 13 mV and a hyperpolarizing shift of the steady-state inactivation (h infinity) curve of about 4 mV. The effects of internal and external OA are broadly similar except that the h infinity shift is not seen with internal application. OS- at concentrations above 2.0 mM produces complete irreversible loss of sodium current. At 2.0 mM, OS- produces 10% current suppression and a small depolarizing shift of the m infinity curve. Internal and external applications of OS- differ little except that external OS- causes a 25% increase in the time constant of activation (tau m). The possible origins of these effects are discussed. It is proposed that the shift of m infinity caused by internal OTMA+ is due to a diminution of the lipid dipole potential at the internal surface of the membrane caused by OTMA+ adsorption. This effect could also account for the m infinity shift caused by OA. The results showing that OA produces shifts of opposite sign in the voltage dependence of m infinity and h infinity are discussed with respect to their implications for models of sodium channel gating.

Action Potentials↗
PubMed1984

Anaesthetic action of esters and ketones: evidence for an interaction with the sodium channel protein in squid axons.

The effects of methyl butyl ketone, methyl heptyl ketone and methyl pentanoate on the sodium current of the squid giant axon have been examined. The peak inward current in intact axons was reduced reversibly by each substance. Sodium currents were recorded in intracellularly perfused axons before and during exposure to the test substances and the records were fitted with equations similar to those proposed by Hodgkin & Huxley (1952). Shifts in the voltage dependence of the steady-state activation and inactivation parameters (m infinity and h infinity), reductions in the peak heights of the activation and inactivation time constants (tau m and tau h) and changes in the maximum sodium conductance (gNa) caused by these substances have been tabulated and compared with the effects of methyl octanoate (Haydon & Urban, 1983b). Each compound shifted the voltage dependence of the steady-state inactivation parameter in the hyperpolarizing direction and that of the steady-state activation parameter in the depolarizing direction. The shifts produced by the ketones are compared with those produced by methyl pentanoate and by methyl octanoate. The possible role of an interaction between the carbonyl oxygen of the test substance and the sodium channel protein in producing the h infinity shift is discussed. The peak time constants are reduced and the voltage dependences of tau m and tau h are shifted in a direction commensurate with the shifts in steady-state properties. The maximum sodium conductance is not much affected either by the ketones or by methyl pentanoate. Large reductions in peak inward current coupled with little effect on gNa have been reported for the n-alkanols and other surface-active compounds (Haydon & Urban, 1983b). This lack of a large effect on gNa indicates that whatever direct interaction does take place between the test substance and the channel protein, it does not result in a blockage of the channel.

Animals↗
PubMed1983

The effects of bilayer thickness and tension on gramicidin single-channel lifetime.

Measurements have been made of gramicidin single-channel lifetimes in monoacylglycerol bilayers chosen so that their thickness ranged from above to below the length of the gramicidin channel. Contact angles, electrical capacities and bulk-phase interfacial tensions have also been determined for these systems. The mean channel lifetime decreased with the hydrocarbon thickness of the membrane until the latter reached 2.2 nm, after which the lifetime was relatively constant. A theoretical model has been proposed which relates the mean channel lifetime (or dissociation constant) to both the thickness and the tension of the bilayers. The analysis of the present results and of those of previous studies has led to the idea that aggregates of water molecules may play an important rôle in the dissociation of the gramicidin channel.

Glycerides↗
PubMed1981

In Vivo Nitrite Reduction in Leaf Tissue of Phaseolus vulgaris L.

Experiments were performed to establish a procedure for in vivo measurement of nitrite utilization by leaf tissue of bean (Phaseolus vulgaris L. cv. Top Crop).To measure light-dependent nitrite disappearance, a single disc of leaf tissue was exposed to light for 1 hour at 30 C while immersed in incubation medium (approximately 0.11 milliliter per square centimeter of leaf area) in the bottom of a tall-form glass beaker. The incubation medium was 100 millimolar phosphate buffer (pH 7.5) with added wetting agent and nitrite. The wetting agent combination of 1% 1-propanol plus 0.05% Neutronyx-600 was used in some experiments for compatibility with established in vivo nitrate reductase (NR) assays; however, 0.05% Neutronyx-600 alone was found to be a suitable substitute. Parallel assays run in the dark on related tissue are recommended as a means to determine the amount of nitrite synthesized within the tissue by the NR system. Adding the results of the two assays gives an estimate of total nitrite utilization by the leaf tissue. It was found that 20 millimolar nitrite in the incubation medium was the most suitable level of external nitrite for promoting light-dependent nitrite disappearance. This was also found to reduce, sometimes to zero, the rate of synthesis of nitrite by NR. NR activity declined steadily with advancing age. Except for very young tissue, the rate of nitrite disappearance was independent of age. Nitrite disappearance was completely blocked by diuron.

Journal Article↗
PubMed1979

The interaction of n-octanol with black lipid bilayer membranes.

The electrical capacities of black lipid films formed from monoolein + n-hexadecane and monoolein + squalane (or squalene) solutions have been measured in the presence of various concentrations of n-octanol. In addition, partition coefficients for n-octanol between n-hexadecane and 0.1 M NaCl, dielectric constants for octanol-hexadecane mixtures and the interfacial tension of films and film-forming lipid solutions against the aqueous phases have been determined. It is concluded that in "solvent-free" bilayers the octanol is unlikely to have changed the bilayer thickness by more than about 1 A. The bilayer tension, on the other hand, increases appreciably in the presence of octanol.

Electrochemistry↗
PubMed1975

Low density lipoprotein cholesterol (CLDL) and lipoprotein phenotyping.

Using an estimation of CLDL, 522 sera from 311 men and 211 women were studied. Lipoprotein phenotyping was done with and without knowledge of CLDL. Two hundred sixty-four of the 522 patients were considered abnormal without knowledge of CLDL. Interpretation was changed in 70 cases when CLDL was considered. Thirty-four were reclassified from 11B to IV because CLDL was not elevated. Thirty-three were reclassified from 11A to "slightly elevated cholesterol without other evidence of hyperlipoproteinemia" because CLDL was not elevated. Three were reclassified from normal to 11A because of elevated CLDL associated with borderline normal cholesterol.

Adolescent↗