PubMed Health⌕ Search

Biomedical subjects

M B MacIver

Publications and source records attributed to M B MacIver.

At least 37 records · Page 2Linked to original sources
PubMed1991

The alpha 2-adrenoceptor agonist dexmedetomidine increases the apparent potency of the volatile anesthetic isoflurane in rats in vivo and in hippocampal slice in vitro.

Alpha 2-adrenoceptor agonists such as clonidine are sedatives and enhance the effectiveness of several different kinds of anesthetics. This study was performed to quantitate the effect of dexmedetomidine, a novel alpha 2-adrenoceptor agonist, on the action of the volatile anesthetic agent isoflurane in rats in vivo. A separate set of experiments in rat hippocampal slices was designed to determine whether isoflurane and dexmedetomidine exerted similar effects on synaptic transmission in vitro and to examine the interaction between the two agents. In vivo, dexmedetomidine (100 micrograms/kg i.p.) reduced isoflurane minimum alveolar anesthetic requirement (MAC), determined by loss of response to tail pinch, by approximately 90%. In hippocampal CA1 neurons, on the other hand, there was a relatively small potentiation of the effects of isoflurane at the maximally effective dexmedetomidine concentration (1 nM). The hippocampal CA1 area, at least in the slice preparation, may thus not be representative of the CNS site(s) at which alpha 2 adrenoceptor agonists lessen anesthetic requirement in vivo.

Adrenergic alpha-Agonists↗
PubMed1991

Halothane enhances tonic neuronal inhibition by elevating intracellular calcium.

Whether the major action of anesthetics is to depress the central nervous system (CNS) by reducing excitation or enhancing inhibition remains unknown. Using whole cell patch-clamp recording in hippocampal slices, halothane and pentobarbital were found to prolong the decay time constant (TAU(D)) of GABAA-mediated spontaneous inhibitory postsynaptic currents (sIPSCs). Intracellular administration of the Ca2+ chelator BAPTA or the Ca2+ release inhibitor dantrolene significantly (ANOVA, P less than 0.005) reduced halothane's effect; in contrast, the pentobarbital effect was unchanged. Halothane induced depression of population spike amplitude was blocked by the GABAA antagonist bicuculline. Together, these findings suggest that a major depressant effect of halothane involves enhancement of GABAA-mediated inhibition through release of intraneuronally stored Ca2+.

Animals↗
PubMed1991

Anesthetic effects on resting membrane potential are voltage-dependent and agent-specific.

Membrane hyperpolarization (increase in resting potential) together with a conductance increase has been suggested as a common mechanism of anesthetic action. The current study compared the effects of halothane, enflurane, and isoflurane on resting membrane potential and conductance of hippocampal CA1 neurons in vitro. At 1 MAC, halothane produced significant (P less than 0.01) hyperpolarization (-2.8 +/- 1.3 mV, mean +/- SD) accompanied by a conductance increase (6.2 +/- 2.7%). Enflurane also produced a significant (P less than 0.001) hyperpolarization (-3.15 +/- 1.2 mV); however, this was accompanied by a conductance decrease (-4.5 +/- 1.5%). Isoflurane produced variable effects. Anesthetic-induced hyperpolarization was maximal in neurons with more negative initial resting potentials and was reduced by depolarization. Across agents, these relatively small changes in resting potential were not correlated with decreases in excitability as measured by synaptically evoked population spike depression. The results are not consistent with a common action of the three agents on a single ionic channel.

Anesthetics↗
PubMed1991

Analgesic concentrations of lidocaine suppress tonic A-delta and C fiber discharges produced by acute injury.

Intravenous lidocaine has been shown to relieve acute postoperative pain and chronic neuropathic pain. It is not known whether analgesia produced by 2-10 micrograms/ml plasma concentrations of lidocaine is due to an effect on peripheral-pain-transducing nerves or to central nervous system effects. The current study examined effects of analgesic concentrations of lidocaine on injury-induced discharge of A-delta and C fibers, using the in vitro rabbit corneal nerve preparation. Lidocaine at concentrations from 1-20 micrograms/ml reversibly suppressed tonic action potential discharge of acutely injured nerves. The median effective concentration (ED50) (5.7 micrograms/ml) corresponds to clinically effective plasma concentrations for analgesia. Electrically evoked nerve conduction was not blocked until lidocaine concentrations were greater than 250 micrograms/ml. Thus, analgesia produced by lidocaine appears to result from suppression of tonic neural discharge in injured peripheral A-delta and C fiber nociceptors.

Animals↗
PubMed1990

Simultaneous visualization and electrophysiology of corneal A-delta and C fiber afferents.

Fluorescent staining of neuronal elements has become an important tool in neuroscience research; however, investigations have been limited by the toxic effects produced by most dyes, especially following excitation by strong epifluorescent illumination. The present study investigated effects produced by the methylpyridinium fluorescent dyes, 4-di-1-ASP and 4-di-2-ASP, on electrophysiologic responses from corneal A-delta and C fiber afferents. Rabbit corneal tissue was isolated and maintained in vitro to facilitate staining, visualization, and electrophysiologic recording of corneal nerves. Nerve fibers were selectively stained by the dyes and could be followed from their point of entry in small nerve bundles at the cornea-sclera border to individual free nerve ending terminals in the corneal epithelium. Neither the dyes nor epifluorescence, alone or in combination, produced any statistically significant changes (P greater than 0.1; t test) in spontaneous discharge activity, spike amplitude, spike dV/dt or stimulus evoked activity in A-delta and C fibers. Epifluorescent visualization of corneal afferents and simultaneous electrophysiologic recording will permit detailed investigations of sensory transduction processes and structure-function relationships in mammalian sensory nerves.

Acetylcholine↗
PubMed1990

Volatile anesthetics excite mammalian nociceptor afferents recorded in vitro.

The present study investigated the actions of halothane, isoflurane, and enflurane on spontaneous discharge and evoked action potential activity in mammalian A-delta and C fiber nociceptors from the in vitro rabbit cornea. At 1 MAC halothane, isoflurane, and enflurane significantly (P less than 0.001) increased spontaneous discharge frequency of C fibers to 410%, 388%, and 569% of control, respectively. The anesthetics produced burst discharge activity over the concentration range of 0.25-1.5 MAC and depressed discharge activity at higher concentrations (greater than 3.0 MAC). Similar excitatory effects were produced by the potassium channel blocker 4-aminopyridine (250-500 microM). Variable effects on evoked discharge activity of A-delta fibers were observed. Halothane reduced action potential amplitude (77.3 +/- 4.5% of control +/- SD; n = 6 at 1 MAC) and increased spike latency (0.42 +/- 0.075 ms). In contrast, the ethers decreased both spike latency (isoflurane by 0.31 +/- 0.064 ms and enflurane by 0.35 +/- 0.058 ms) and action potential amplitude. Halothane and the ether anesthetics produced a common excitatory action on C fibers; however, the differential depressant effects on A-delta fibers suggest that different membrane mechanisms of action are involved.

4-Aminopyridine↗
PubMed1989

General anaesthetic modification of synaptic facilitation and long-term potentiation in hippocampus.

The synaptic integrative properties of facilitation and potentiation are important determinants of cortical neurone excitability. The present study measured the effects of halothane and methoxyflurane on synaptic facilitation, paired-pulse potentiation, and long-term potentiation (LTP) in CA1 pyramidal neurones of rat hippocampal slices. Methoxyflurane 0.16vol% and halothane 1.2 vol% depressed population spike amplitudes by approximately 100%, but halothane did so with relatively little (less than 10%) depressant effect on the field excitatory postsynaptic potential (EPSP). Both agents enhanced EPSP facilitation, halothane more than methoxyflurane. Halothane consistently enhanced paired-pulse population spike potentiation; methoxyflurane sometimes diminished it. Halothane reduced the probability of LTP induction to an extent correlated with block of population spike responses in the inducing stimulus train (r = 0.92); methoxyflurane did not block LTP. The results suggest that these agents affect cortical excitability by multiple actions, the distribution of actions being specific to each agent.

Animals↗
PubMed1989

Enflurane-induced burst discharge of hippocampal CA1 neurones is blocked by the NMDA receptor antagonist APV.

The basis for the hyperexcitability and seizure activity associated with enflurane anaesthesia was investigated using extracellular and intracellular recording in rat hippocampal brain slices. Enflurane produced seizure-like burst discharges in CA1 pyramidal neurones, accompanied by depressed field potential amplitudes and a reduced threshold for synaptically evoked population spikes. However, threshold for action potentials evoked by intracellular current injection did not change, nor did action potential amplitude, duration or spike frequency accommodation in single neurones. Enflurane 2.0 vol% hyperpolarized CA1 neurones (3.1 (SD 1.3)mV), decreased membrane conductance (12 (6)% below control), and depressed EPSP amplitudes (34% of control) (P less than 0.01). Enflurane appeared to enhance both intrinsic and synaptically mediated inhibitory potentials. The N-methyl-D-aspartate (NMDA) receptor antagonist amino-phosphonovalerate (APV) 5-20 mumol litre-1 completely blocked seizure-like burst discharge of CA1 neurones in the presence of enflurane, and the enflurane-induced reduction of population spike threshold; it did not alter anaesthetic depression of EPSP amplitude. Thus enflurane-induced burst discharge of CA1 neurones appeared to involve an enhancement of excitatory synaptic transmission rather than depression of intrinsic or synaptic inhibition.

2-Amino-5-phosphonovalerate↗
PubMed1988

Inhalation anaesthetics exhibit pathway-specific and differential actions on hippocampal synaptic responses in vitro.

The effects of halothane, isoflurane and enflurane were compared on three CNS excitatory synaptic pathways in vitro, to determine whether selective actions described in vivo result from differential effects on anatomically distinct cortical pathways and neurone populations. Halothane (0.25-1.25 vol%) depressed postsynaptic excitability of CA1 pyramidal neurones in response to activation of stratum radiatum synaptic inputs, and concentration-dependent excitatory (0.25-1.25 vol%) and depressant (1.5-2.0 vol%) actions were observed on dentate granule neurone excitability and perforant path evoked synaptic responses. In contrast, isoflurane increased CA1 neurone excitability (0.25-0.75 vol%) and produced postsynaptic depression of dentate neurones (0.5-4.0 vol%). Enflurane also increased CA1 excitability (0.5-4.0 vol%), but depressed synaptic responses at equivalent concentrations, and produced mixed excitatory (0.25-1.0 vol%) and depressant (1.0-4.0 vol%) effects on dentate synaptic responses. Differential actions were also observed for the three anaesthetics on stratum oriens excitatory inputs to CA1 neurones, and on antidromic responses. A good correlation (r = 0.992) exists between the membrane/buffer partition coefficients of these anaesthetics and their half-maximal concentrations for depression of synaptic responses; however, this correlation does not reflect the different, anaesthetic-specific actions observed. The results indicate that inhalation anaesthetics act at multiple and selective hydrophobic recognition sites which are heterogenously distributed on different synaptic pathways.

Action Potentials↗
PubMed1988

Pressure reversal of anaesthesia: a synaptic mechanism.

Hyperbaric pressure induces seizures and increases anaesthetic requirements ("pressure reversal of anaesthesia"), but both pressure and anaesthetic agents depress excitatory synaptic transmission. The present study has attempted to resolve this paradox. The interaction between helium pressure to 10.1 MPa and anaesthetic agents (pentobarbitone, halothane, methoxyflurane) was investigated at a crustacean glutaminergic excitatory neuromuscular junction which can be modulated by GABA inhibition. Both pressure and the anaesthetics depressed the singly evoked excitatory junctional potential (EJP). During repetitive stimulation, both pressure and pentobarbitone antagonized their own depressant effects by enhancing tetanic potentiation. The additive enhancement at 10.1 MPa was sufficient to increase the pentobarbitone-depressed response above the corresponding normobaric level. No significant antagonism between pressure and any of the anaesthetics was observed on the properties of EJP amplitude and time course, facilitation, potentiation or inhibition. Additivity rather than antagonism is the basis for pressure reversal of anaesthetic depression at this model synapse. The functional antagonism is therefore indirect, and probably involves multiple sites of action for both pressure and anaesthetics.

Action Potentials↗
PubMed1987

Cholinergic theta rhythm in transected hippocampal slices: independent CA1 and dentate generators.

The controversy concerning intrahippocampal theta (theta) generators, arising as a result of in vivo investigations, prompted us to record theta-activity from isolated populations of CA1 pyramidal or dentate granule neurons in vitro. In the present study, transected slices (trans-slices) of the hippocampal formation were used to isolate the CA1 area from the dentate gyrus, providing a method for testing the 'two generator' hypothesis. We demonstrated that neurons in both the CA1 area and dentate gyrus could independently generate carbachol-induced (type 2) electroencephalogram (EEG) theta-activity. This activity could be completely blocked by the muscarinic receptor antagonist atropine sulfate but was unaffected by the nicotinic blocker, (+)-tubocurarine. These in vitro results provide the first direct evidence for the two-generator hypothesis and confirm the cholinergic-muscarinic nature of type 2 slow wave theta.

Animals↗
PubMed1987

Anesthetics produce differential actions on membrane responses of the crayfish stretch receptor neuron.

The actions of ethanol, halothane and pentobarbital on the membrane electrical properties and synaptic transmission of isolated crayfish stretch receptor neurons were studied to determine possible sites of action contributing to differential effects previously described on physiological discharge activity. The three agents depressed GABA-mediated transmission and altered postsynaptic membrane electrical properties. Both pre- and postsynaptic sites of action appeared to contribute to the anesthetic-induced alteration of neuronal function. The agents studied produced different, concentration-dependent, membrane effects which included biphasic actions on membrane resistance and spike threshold. The results suggest that multiple-sites of action are involved and different anesthetics may not act via the same mechanism(s) at these sites.

Anesthetics↗
PubMed1987

Anesthetics produce differential actions on the discharge activity of a single neuron.

The effects of 26 anesthetic agents were studied on the rhythmical discharge activity of a single isolated neuron (crayfish stretch receptor). Many of these agents produced concentration-dependent biphasic responses (excitation and depression), and some also induced altered discharge patterns (burst activity). The dominant effect of a few of the anesthetics was excitation (e.g. alphaxolone); depression (e.g. decanol); or burst activity (e.g. benzocaine). A correlation was found to exist between equieffective concentrations in the perfusate and membrane/buffer partition coefficients; however, this general phenomenon does not provide an explanation for the biphasic or differential responses. These results demonstrate that selective interactions occur at the level of the single neuron, and suggest the existence of recognition sites in neuronal membranes which can discriminate structural differences of anesthetics.

Action Potentials↗
PubMed1987

Carbachol-induced EEG 'theta' activity in hippocampal brain slices.

Application of the cholinergic agonist carbachol (50 microM) produced theta-like rhythmical waveforms, recorded in the stratum moleculare of the dentate gyrus. Atropine sulfate (50 microM) antagonized the carbachol-induced theta-like activity, consistent with this action of atropine in vivo. These results provide the first direct evidence that hippocampal neurons are capable of producing synchronized slow-wave activity when isolated from pulsed rhythmic inputs of the medial septum and other brain regions.

Animals↗
PubMed1987

Enflurane-induced burst firing of hippocampal CA 1 neurones. In vitro studies using a brain slice preparation.

Enflurane can produce seizure activity in the cortical EEG, in vivo, at concentrations associated with surgical anaesthesia. The present study was designed to determine whether this seizure-like burst activity could occur in isolated cortical neurones. Enflurane altered synaptic transmission in the in vitro rat hippocampal slice preparation and produced seizure-like burst discharges of CA 1 neurones, at vapour concentrations equivalent to those obtained during anaesthesia (2-6 vol%; 0.5-1.5 mmol litre-1). Burst discharges occurred both spontaneously and in response to stimulation of stratum radiatum fibres in the CA 1 pyramidal region, but not in the dentate area. Low concentrations of enflurane (approx. 0.75 mmol litre-1), decreased the field potential responses of CA 1 neurones; however, dentate granule neurone responses were increased. Input/output analyses of field excitatory post-synaptic potential (EPSP) and population spike amplitudes revealed that the enflurane-induced depression of field potential responses was associated with decreases in synaptic input, whereas burst activity resulted from a decrease in the threshold of CA 1 neurones.

Action Potentials↗