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A G Macdonald

Publications and source records attributed to A G Macdonald.

At least 19 recordsLinked to original sources
PubMed1995

The effects of nitrous oxide on a glutamate-gated ion channel and their reversal by high pressure; a single channel analysis.

Nitrous oxide reversibly affects the kinetics, but not the conductance, of the qGluR channel of locust muscle. 0.5 atm N2O at 20.5 degrees C was without effect but both 1.5 and 2.7 atm significantly reduced the probability of the channel opening, the frequency of opening and the mean open time, and prolonged the mean closed time. 100 atm helium was without effect on these parameters, but when 98.5 atm He was combined with 1.5 atm N2O they, and the associated dwell time distributions, were restored to normal. 100 atm similarly combined with 2.7 atm N2O exerted a comparable trend which fell short of significance. The results are consistent with nitrous oxide binding to the channel with a significant molar volume increase, which pressure opposes. This suggests that nitrous oxide may cause conformational changes in the channel, and that the pressure reversal of nitrous oxide anaesthesia in animals could be caused by molecular antagonism.

Animals↗
PubMed1993

Effects of high pressure on the channel gated by the quisqualate-sensitive glutamate receptor of locust muscle and its blockade by ketamine; a single-channel analysis.

The effects of high pressure on the channel gating kinetics of the quisqualate-sensitive L-glutamate receptor (qGluR) of locust muscle have been investigated using a megaohm seal patch-clamp technique. Pressure was applied with helium gas and recordings were carried out at 20.5 degrees C with Rb+ as the main charge-carrying cation in the patch pipette. The mean open time of the qGluR channel was unaffected by 10 and 30 MPa, but it was significantly reduced at 50 MPa. A high proportion of brief openings (mean 0.808 ms) was seen at 50 MPa but not at lesser pressures. Also, in contrast to lesser pressures, 50 MPa prolonged the mean closed time and reduced both the frequency and probability of channel opening. 10(-6) M ketamine significantly reduced the mean channel open time, as previously reported. A pressure of 10 MPa which alone had no effect on the qGluR channel, restored the mean open time in the presence of 10(-6) M ketamine to the value obtained in the absence of the anaesthetic. This implies the shortening of qGluR channel open time by ketamine involves a large + delta V and, therefore, probably conformational changes in the channel. However 10 MPa did not restore the distribution of open times to normal.

Animals↗
PubMed1992

Homeoviscous adaptation under pressure: the pressure dependence of membrane order in brain myelin membranes of deep-sea fish.

Steady-state and time-resolved anistropy of 1,6-diphenyl-1,3,5-hexatriene (DPH) fluorescence have been used to compare the hydrocarbon order of brain myelin membranes from a shallow water (plaice) and two deep-sea fish species (Coryphenoides rupestris and Coryphenoides armatus). At atmospheric pressure the deep sea fish displayed lower steady-state anisotropies than shallow water species although the pressure dependence of anisotropy was similar in all species. Time-resolved measurements allowed the separate determination of the rate of probe motion from the amplitude of that motion. Anisotropy decays were analysed in terms of two correlation times and a constant (r infinity). The r infinity and mean value of P2 order parameter for all species increased with pressure, the graphs for deep-sea species being translated to higher pressures relative to shallow-water species. The resulting pressure coefficients for C. armatus was distinctly less than for the two shallower species. These time-resolved studies show that the interspecific differences provide for similar order parameters in all three species when corrected to their respective habitat conditions of pressure and temperature. This indicates that myelin order is highly conserved despite the profound ordering effects of high hydrostatic pressure.

Adaptation, Physiological↗
PubMed1992

Single channel analysis of ketamine interaction with a quisqualate receptor.

The interactions of the general anaesthetic ketamine with the quisqualate-sensitive L-glutamate receptor (QUIS-R) of locust muscle have been investigated at the single channel level using a M omega seal patch clamp technique. Low concentrations (10(-10) to 10(-9) M) of ketamine did not significantly alter the kinetics of the QUIS-R channel. Higher concentrations of ketamine decreased the probability of the channel being open, the frequency of channel opening and the channel mean open time, and increased the channel mean closed time. Probability density functions of channel dwell times indicate that during application of greater than 10(-8) M ketamine the distribution of channel openings becomes restricted mainly to brief events. These results are consistent with the view that ketamine blocks the open, and possibly also the closed, channel of locust muscle QUIS-R and that this anaesthetic dissociates only slowly from its blocking site(s).

Animals↗
PubMed1990

Behavioural thermoregulation in mice: effects of low doses of general anaesthetics of different potency.

Chloroform, monochlorodifluoromethane and nitrous oxide produced dose-related decreases in the rectal temperatures of mice allowed to choose between a warm and a cool environment. The doses used were subanaesthetic, respectively 0.0013-0.004, 0.028-0.085 and 0.25-0.5 atm. The hypothermia (up to 3.6 degrees C) was usually associated with significant reductions in time spent in the warm. The log dose-hypothermic response plots were approximately parallel and there was a marked correlation between anaesthetic potency, as measured by the abolition of the righting response, and hypothermic potency.

Anesthetics↗
PubMed1990

Effects of hydrostatic pressure and inert gases on platelet aggregation in vitro.

A novel cuvette was used to subject citrated platelet-rich plasma (PRP) to high hydrostatic pressure with negligible contamination by He (used for compression of the apparatus). Aggregation was induced at pressure by ADP and quantified turbidimetrically. The maximum degree of aggregation (MDA) was reduced from a control level of 82.2 to 53.6% by exposure to 101 ATA. Because decompression bubbles did not form, aggregation was also measured immediately after a compression cycle. After exposure to 101 ATA hydrostatic pressure, platelets responded normally to ADP at 1 ATA. In a matching apparatus, PRP was equilibrated with high partial pressures of inert gases. Normal physiological plasma Po2 and pH were maintained during equilibration. N2O (5 ATA) reduced the MDA from 86.5 (control) to 58.1%. N2 (51 ATA) reduced the MDA from 74.7 (control) to 51.6%, and 101 ATA Pn2 reduced the MDA from 78.0 (control) to 32.3%. He (100 ATA) reduced the MDA from 83.6 to 38.6%. It was concluded that platelet aggregation was relatively sensitive to hydrostatic pressure and less sensitive to inert gases than predicted from their anesthetic potency ratios.

Adenosine Diphosphate↗
PubMed1989

The adaptation of biological membranes to temperature and pressure: fish from the deep and cold.

The homeostatic regulation of bilayer order is a property of functional importance. Arguably, it is best studied in those organisms which experience and must overcome disturbances in bilayer order which may be imposed by variations in temperature of hydrostatic pressure. This article reviews our recent work on the adaptations of order in brain membranes of those fish which acclimate to seasonal changes in temperature or which have evolved in extreme thermal or abyssal habitats. The effects of temperature and pressure upon hydrocarbon order and phase state are reviewed to indicate the magnitude of the disturbances experienced by animals in their environments over the seasonal or evolutionary timescale. Acclimation of fish to altered temperature leads to a partial correction of order, while comparison of fish from extreme cold environments with those from temperate or tropical waters reveals a more complete adaptation. Fish from the deep sea also display adaptations of bilayer order which largely overcome the ordering effects of pressure.

Adaptation, Physiological↗
PubMed1989

Behavioral thermoregulation in mice subjected to high pressure.

Mice exposed to normoxic He and Ne at increased pressure and allowed to choose between a neutral and a cool environment showed a preference for the cooler environment. This behavior was apparent at 5.7 but not at 2.5 atm He. At 11.3 atm He and Ne, the behavior was associated with a similar reduction in the deep body temperature to a new steady level. The reduction in body temperature increased with pressure, up to 35 atm He, the maximum studied. Since the heat transfer of the He and Ne gas mixtures is different and both gases exert negligible anesthetic effects, the hydrostatic pressure most likely affects behavioral thermoregulation by affecting neuronal function.

Animals↗
PubMed1988

Temperature, pressure and cholesterol effects on bilayer fluidity; a comparison of pyrene excimer/monomer ratios with the steady-state fluorescence polarization of diphenylhexatriene in liposomes and microsomes.

Pyrene excimer/monomer (E/M) ratios have been compared with the steady-state fluorescence polarization (P) of diphenylhexatriene (DPH) in multilamellar liposomes of dilaurylphosphatidylcholine and rat liver microsomes. The purpose was to use the well-understood properties of DPH to reveal the nature of bilayer fluidity which pyrene manifests as an E/M ratio. Reducing the temperature (from 37 degrees C to 8 degrees C), increasing the hydrostatic pressure (from 0.1 to 70 MPa), and, in liposomes, cholesterol enrichment (up to 0.30 mole fraction) separately decreased the E/M ratios and increased P. The pyrene membrane/buffer partition coefficient was affected by temperature but not by pressure, and in the case of cholesterol enrichment, it was assumed to be unaffected. Plots of P as a function of the E/M ratio showed the two to be closely correlated (r = 0.99 in liposomes and 0.96 in microsomes), independent of the treatment used to reduce fluidity. The apparent activation volume and enthalpy for excimer formation was calculated and compared with published data. Pyrene E/M ratios probably reflect the intermolecular volume (fluidity) of the outer region of the bilayer, which is reduced by a decrease in temperature and an increase in pressure and cholesterol. DPH reports the bilayer interior, which is similarly ordered by the experimental treatments. The regional distinction between the two probes, however, accounts for the divergence of E/M ratios and P, which has been reported in membranes enriched with fluidizing fatty acids.

Animals↗
PubMed1988

Effect of the preoperative administration of water on gastric volume and pH.

Since the preoperative administration of water might promote gastric emptying and dilute the remaining gastric contents, 50 patients were investigated before elective surgery. One group was given water 100 ml 2 h before operation; the other group was fasted as usual. Volume and pH of gastric contents were measured immediately after the induction of anaesthesia. Although the mean gastric residue was less in those patients who were given water, the differences were not statistically significant. There was no difference in gastric pH between the two groups.

Adult↗
PubMed1987

Effects of hydrostatic pressure on the motor activity of fish from shallow water and 900 m depths; some results of Challenger cruise 6B/85.

1. Two species of benthic fish from 900 m depths (90 atm pressure), Trachyscorpia cristulata echinata and Synaphobranchus kaupi, are shown to be adapted to their normal, high ambient pressure. 2. Their condition improves when they are restored to their normal pressure after experiencing decompression in a trawl and they undergo convulsions at 150 atm. 3. This contrasts with the response of shallow water species (Salmo salar, Pleuronectes platessa, Anguilla anguilla and Gadus morhua) which convulse at 93-114 atm and become immobilized and rigid at 150 atm.

Animals↗
PubMed1987

The effect of pressure on the lateral swimming muscle of the European eel Anguilla anguilla and the deep sea eel Histiobranchus bathybius; results of Challenger cruise 6B/85.

1. The viability of Histiobranchus lateral muscle was prolonged up to 7 times by recompression of the tissue. 2. The maximum twitch contraction force of both Anguilla and Histiobranchus was recorded at a pressure between 150 and 350 atm. At 1 atm Anguilla developed 60% maximum force and Histiobranchus 10-20% maximum force. 3. Twitch contraction time doubled for a pressure increase of 400 atm. This effect is predicted to halve the maximum swimming speed at 4000 m and is discussed in relation to muscle force and anaerobic support.

Anguilla↗
PubMed1986

Effects of subanesthetic doses of inert gases on behavioral thermoregulation in mice.

Mice exposed to subanesthetic partial pressures of N2O (0.25 to 0.75 atm) or N2 (5.7 or 11.33 atm) and allowed to choose between a warm and a cool environment showed a marked preference for the cooler environment. This behavior was associated with the onset of hypothermia, with deep body temperature falling by up to about 3 degrees C, usually to a new, steady level. Both the length of time spent in the cooler environment and the degree of the hypothermia produced increased with the partial pressure of N2O or N2 used. The effects of N2O on behavioral thermoregulation and body temperature were reversible. There was a correlation between anesthetic potency and the ability of both gases to alter thermoregulation, suggesting that the effect of these agents on thermoregulation was caused by the same molecular interactions as those which underlie anesthesia. Since both gases elicited changes in behavioral thermoregulation promoting rather than opposing the onset of hypothermia, it is concluded that they may have acted to lower the level at which deep body temperature was being regulated.

Anesthetics↗
PubMed1986

Effects of high pressure on platelet aggregation in vitro.

An apparatus which enables aggregating agents to be added to a stirred suspension of platelets subjected to a pressure of up to 600 ATA is described. The ensuing aggregation reaction is monitored optically. The pressure is applied with helium; data are presented that indicate the effects are mainly attributable to hydrostatic pressure. The aggregation of human platelets induced by ADP was reversibly inhibited by pressure in the 1-270 ATA range. The second phase of aggregation was blocked by 65 ATA; the rate of first phase aggregation was reduced but the time to respond to ADP was not affected. Comparable pressures also affected collagen and arachidonate-induced aggregation. The time to respond to these aggregating agents was prolonged and both the rate and the degree of aggregation were reduced by pressure.

Adenosine Diphosphate↗