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Biomedical subjects

J D Lambert

Publications and source records attributed to J D Lambert.

At least 73 records · Page 4Linked to original sources
PubMed1984

The response of cat spinal motoneurones to the intracellular application of agents with local anaesthetic action.

QX-222 (the trimethyl analogue of lignocaine), methylxylocholine, lignocaine and pentobarbitone were iontophoresed intracellularly into cat lumbosacral motoneurones. Iontophoresis and recording was either from a triple-barrelled microelectrode unit or from two separately advanced microelectrodes. QX-222 and methylxylocholine caused a very slow reversible block of the current-evoked and antidromic action potentials (AP) with no significant change of membrane potential (EM). Lignocaine had a minimal blocking effect on the AP. No change, or only a small decrease, of membrane slope conductance (GM) was seen when the APs had been totally abolished. QX-222 and methylxylocholine reduced the massive GM increase evoked by the passage of large depolarizing currents and converted the post-current hyperpolarization (time constant 120-150 ms) into a depolarization of similar time course. It is suggested that the quaternary local anaesthetics can reduce the fast and slow voltage-dependent potassium conductances. Both agents totally blocked AP generation without decreasing the magnitude of the Ia e.p.s.p. It is suggested that intracellularly iontophoresed QX-222 (on account of its low lipid solubility) could be used as a pharmacological tool to block specifically the active Na and channels in only the cell impaled by the microelectrodes.

Action Potentials↗
PubMed1983

The interaction of the beta-carboline derivative DMCM with inhibitory amino acid responses on cultured mouse neurones.

Benzodiazepine (BZ) and GABA receptors are associated in the neuronal membrane. GABA responses are enhanced in the presence of BZs. The convulsant DMCM (methyl 6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate), like other beta-carbolines, binds with high affinity to BZ receptors. The effects of DMCM and of the BZ midazolam, on GABA responses, were studied in mouse cultured neurones using intracellular recording techniques. GABA responses were usually reduced by DMCM and potentiated by midazolam. This, with an occasional direct facilitatory effect on the membrane, is consistent with the convulsive action of DMCM.

Animals↗
PubMed1982

Reversibility of Ia EPSP investigated with intracellularly iontophoresed QX-222.

1. Cat lumbosacral motoneurons were impaled by two individually advanced microelectrodes: one to record membrane potential (EM), the second to pass depolarizing currents. 2. During the passage of depolarizing current ramps the repetitive action-potential firing and the later high conductance (GM) state obscured and distorted Ia excitatory postsynaptic potentials (EPSPs) evoked by electrical stimulation of hindlimb muscle afferents. 3. Intracellular iontophoresis of QX-222 (a trimethyl analogue of lignocaine) or methylxylocholine, prevented action-potential generation and reduced the GM increase during current depolarization so that positive levels of EM could be reached. 4. Following QX-222 treatment it was possible to demonstrate a reversal of the Ia EPSP including its first part, at EM values between -13 and +32 mV. Reversal was seen in 13 of the 22 motoneurons tested. 5. Reversal was easiest to obtain in motoneurons of the deep peroneal group. More positive levels of EM were needed to show a reversal in neurons of the gastrocnemius-so-leus group. (The 10-90% rise times of the EPSPs were rather similar for both groups.) 6. In a few motoneurons the initial part of the Ia EPSP reversed at a more negative EM than a later part. This was best seen after subtraction of the extracellular field potentials from the records.

Animals↗
PubMed1979

Sustained extracellular potentials in the cat spinal cord during the microiontophoretic application of excitatory amino acids.

Sustained negative potentials were recorded in the ventral horn of the cat spinal cord during current balanced extracellular iontophoresis of excitatoyr amino acids. The potentials (referred to a distant indifferent electrode) were measured by an extracellular microelectrode. These focal potentials (FPs) were evoked by DL-homocysteate, L-glutamate, N-methyl-D-aspartate and kainate. These FPs are not an artifact of extracellular microiontophoresis. Their time course is correlated with the depolarization of spinal motoneurones by excitatory amino acids. During iontophoresis of kainate, FPs can be as large as 50 mV and can be recorded for up to 1 mm from the site of drug application. The FP and depolarization caused by kainate were usually irreversible. The depolarization of motoneurones evoked by excitatory amino acids is very much larger when recorded as a 'transmembrane potential' (i.e. the potential of an intracellular electrode minus the potential of a local extracellular electrode) rather than as a 'classical' intracellular potential (i.e. referred to a distant reference electrode). Possible mechanisms for the generation of the FP are discussed. It is suggested that FP may be recorded routinely during microiontophoretic studies employing extracellular recording of neuronal activity. The application of the FP as a measure of cell depolarization during pharmacological studies of excitatory amino acids and agents that block their action is discussed.

Amino Acids↗
PubMed1979

A comparison of extracellular and intracellular recording during extracellular microiontophoresis.

A technique is described in which a central recording microelectrode can be moved independently of a concentrically arranged multibarrelled electrode prepared for microiontophoresis. Recordings were made from cat spinal motoneurones during microiontophoretic applications of excitatory amino acids and biogenic amines with the central electrode placed first extracellularly and then intracellularly. Recording were also made from one of the iontophoretic barrels. Both intra- and extracellular electrodes were used to record action potential firing, the ventral root field (VRF) evoked by antidromic ventral root stimulation and the membrane potential (EM). They were also used to record 'focal potentials' evoked by the extracellular application of drugs to nearby neurones. The firing pattern evoked by extracellular iontophoretic applications of DL-homocysteate and glutamate was not altered significantly following impalement of the cell by the recording microelectrode. Excitatory amino acids usually caused a reduction of the VRF negative wave and evoked an additional late positive wave. These VRF changes recovered at the same rate as the extracellularly recorded, negative 'focal potentials' (Flatman and Lambert, 1979). Iontophoretic applications of biogenic amines caused small increases, small decreases, or no change of the VRF negative wave. Variable responses were also seen during intracellular recording: hyperpolarization, no response and, occasionally, depolarizations were recorded. It is concluded that, during the drug action, VRF changes are difficult to interpret and are a poor index of drug-evoked changes in neuronal excitability or EM.

Amino Acids↗
PubMed1979

The actions of excitatory amino acids on motoneurones in the feline spinal cord.

1. Combined recording or ionophoretic electrodes of the concentric type were used to investigate the depolarizing responses of DL-homocysteate (DLH) and L-glutamate in cat lumbar motoneurones. 2. Typically, DLH responses were slow both in onset and recovery, while glutamate responses were fast in onset and recovery and were frequently accompanied by a post-response hyperpolarization. 3. DLH responses (smaller than those necessary to evoke firing) were accompanied by a stable decrease in GM. This decrease was usually more than could be accounted for by anomalous rectification of the membrane. 4. Small glutamate responses were accompanied by either a small decrease, no change or a small increase in GM. There was a biphasic change in GM during large responses: GM decreased during the rising phase and early part of the response plateau and thereafter increased as the depolarization was maintained. It is proposed that the high conductance state during glutamate application (but not the depolarization itself) is a manifestation of glutamate uptake. 5. Firing evoked by DLH was stable during very long applications of the drug. Firing evoked by glutamate was usually of short duration, despite the maintained depolarization. 6. No reversal potential for the DLH responses could be demonstrated, but the responses decreased in size both with hyperpolarization and depolarization of the membrane. A 'null point' of the response in the negative direction was found to be approximately -95 mV. 7. DLH resonses were insensitive to changes in the internal Cl concentration. When the external K concentration was increased by K+ ionophoresis, the DLH responses became smaller. It is concluded that the DLH response is probably mediated via a decrease in K+ conductance and that the availability of this conductance channel is potential dependent. 8. Changes in the sizes of evoked potentials (e.p.s.p.s, i.p.s.p.s and a.h.p.s) with DLH and glutamate responses were investigated. The size of each of these evoked potentials was inversely related to GM during the responses; thus they all showed stable increases during DLH responses. E.p.s.p.s recorded during DLH were of longer half-width and time-to-peak than the control, but there was no change in the maximum slope (V.sec-1). When e.p.s.p.s decreased in size with glutamate the time-to-peak remained constant. 9. Acidic amino acids have been implicated as natural excitatory transmitters. The consequence of our results for the mechanism of excitatory transmission is therefore discussed.

Action Potentials↗