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Biomedical subjects

R A Davidoff

Publications and source records attributed to R A Davidoff.

At least 55 records · Page 3Linked to original sources
PubMed1984

Spontaneous dorsal root potentials arise from interneuronal activity in the isolated frog spinal cord.

Spontaneous dorsal root potentials (sDRPs) were recorded from the dorsal roots of the isolated frog spinal cord using sucrose gap techniques. sDRPs were always negative (depolarizing) in sign and ranged in size from about 100 microV to 6.0 mV. The largest sDRPs were 25-40% of the amplitude of DRPs evoked by stimulation of adjacent dorsal roots. Hypoxia or accumulation of extracellular K+ ions did not appear responsible for the generation of this spontaneous activity since exposing the cord to unoxygenated Ringer's solution decreased sDRPs and K+-sensitive microelectrodes indicated that only small changes in extracellular K+ (approximately 0.15 mM) were produced coincidently with the largest sDRPs. Chemically-mediated synaptic transmission was found to be necessary for the production of sDRPs because the addition of Mn2+ or Mg2+ ions or tetrodotoxin to the Ringer's solution or reduction of its Na+ concentration blocked sDRPs, whereas application of 4-aminopyridine enhanced them. It did not seem that a direct action of GABA on afferent fiber terminals was responsible for the generation of spontaneous potentials since an increase in sDRPs was seen after: application of the GABA antagonists, bicuculline and picrotoxin; exposure to the glutamic acid decarboxylase inhibitor, semicarbazide (which significantly reduced the concentration of GABA in the cord); and lowering of the external Cl- concentration. Similarly taurine is probably not significant since the taurine antagonist, TAG, increased the amount of spontaneous activity. On the other hand, (--)-baclofen, which is thought to reduce excitatory amino acid release, D,L-alpha-aminoadipic acid, alpha, epsilon-diaminopimelic acid, and 2-amino-4-phosphonobutyric acid, which are believed to be selective postsynaptic excitatory amino acid antagonists, and [D-Pro2-D-Phe7-D-Trp9]-substance P, a postsynaptic blocker of the action of substance P, markedly and reversibly reduced sDRPs. Experiments were performed on isolated cords without supraspinal or afferent input; therefore sDRPs must be generated by intraspinal structures. It would seem that interneurons are responsible because addition of mephenesin or pentobarbital--compounds which inhibit polysynaptic reflex transmission involving interneurons--reduced the production of sDRPs. sDRPs may result from the action of excitatory transmitters such as L-glutamate, L-aspartate, or substance P released by interneuronal firing in the spinal cord. Moreover, because sDRPs were increased by application of yohimbine, corynanthine and propanolol and reduced by haloperidol, such interneurons may be under descending control of adrenergic and dopaminergic fibers.

Afferent Pathways↗
PubMed1984

Spinal seizures and excitatory amino acid-mediated synaptic transmission.

In the isolated frog spinal cord penicillin or strychnine produced spinal seizures with spontaneous slow paroxysmal ventral root depolarizations (pVRDs) and superimposed motoneuron spikes. Mn2+, tetrodotoxin, mephenesin and low [Na+]o suppressed pVRDs, an indication that paroxysmal activity requires intact excitatory synaptic transmission involving interneurons. Compounds reducing the release of amino acids [-)baclofen) or interfering with the activation of N-methyl-D-aspartic acid (NMDA) receptors (D,L-alpha-aminoadipate, D-2-amino-5-phosphonovalerate, gamma-D-glutamylglycine) eliminated pVRDs. The results suggest that synaptic release of excitatory amino acids (e.g. L-glutamate, L-aspartate) and subsequent activation of specific receptors sensitive to the action of NMDA underlie spinal convulsions.

Afferent Pathways↗
PubMed1983

Catecholamine effects on frog dorsal root terminals.

Dopamine, norepinephrine and epinephrine applied to the isolated superfused frog spinal cord had complex effects on the terminals of primary afferent fibers. The most consistent finding was a slow hyperpolarization of terminals with lower concentrations (10 microM or lower), but depolarizations either following or admixed with the hyperpolarizations were seen. These were particularly prominent when the catecholamines were applied in high concentrations or for prolonged periods of time. A part of the response of afferent terminals appears to be indirect since the potential changes were reduced following exposure of the cord to tetrodotoxin, Mn2+, or mephenesin. The hyperpolarizations were augmented by imipramine, a known inhibitor of catcholamine uptake. These observations are consistent with a role of catecholamines in the processing of sensory input in the spinal cord.

Animals↗
PubMed1982

GABA 'desensitization' of frog primary afferent fibers.

GABA (gamma-aminobutyric acid) depolarizes the terminals of primary afferent fibers of the in vitro hemisected frog spinal cord. During sustained or repetitive exposure to GABA or to muscimol, the amplitude of the depolarization is characterized by a rapid and exponential decline to a steady plateau level (desensitization). Desensitization to muscimol was eliminated by removal of Ca2+ and addition of Mn2+ to the superfusate--a finding consistent with the presence of 'receptor' ('true') desensitization (i.e., receptor inactivation). GABA desensitization was significantly reduced by exposure of the cord to either low Na+, low temperature, ouabain, dinitrophenol, (+/-)-nipecotic acid, or cis-1,3-aminocyclohexanecarboxylic acid. These treatments also significantly decreased the high affinity uptake of GABA when the latter process was studied by incubating frog spinal slices in Ringer's solution containing a low concentration of [3H]GABA. These results suggest that cellular transport processes can influence the form of GABA responses and indicate that neuronal removal of GABA is responsible in part for GABA desensitization.

Afferent Pathways↗
PubMed1982

Excitatory amino acids and potassium release in the frog spinal cord.

Synaptic release of excitatory amino acids such as L-glutamate and/or L-aspartate and subsequent activation of specific receptors by these putative transmitters appears necessary for the release of K+ by afferent stimulation in the isolated frog spinal cord. This conclusion is based on the findings that (-)baclofen, which is thought to reduce the presynaptic release of putative excitatory amino acid transmitters, and some amino dicarboxylic amino acids (D, L-alpha-aminoadipic acid, 2-amino-4-phosphonobutyric acid, and D, L-alpha, epsilon-diaminopimelic acid), which are believed to interfere with the activation of receptors by these same excitatory amino acids, significantly attenuate the increment in extracellular K+ evoked by tetanic dorsal root stimulation.

Afferent Pathways↗
PubMed1981

The presynaptic effects of valproic acid in the isolated frog spinal cord.

The effects of the anticonvulsant valproic acid (n-dipropylacetate, DPA) on frog primary afferent fibers was examined with sucrose gap recordings from the dorsal roots. Addition of DPA to the superfusate consistently reduced the amplitude and duration of the dorsal root potential. In contrast, DPA augmented the depolarization of dorsal roots produced by GABA, beta-alanine and taurine. It also decreased afferent fiber 'desensitization' to GABA. DPA depressed the ability of K+ and the excitatory amino acids glutamate and aspartate to depolarize afferent fibers. In addition, the compounds decreased the amount of K+ released by tetanic stimulation of the dorsal root. The K+-evoked release of tritiated GABA from cord slices was initially reduced by exposure to DPA, but was then unaffected after a longer application of the anticonvulsant. On the other hand, the high affinity uptake of tritiated GABA and glycine were almost totally blocked by the addition of DPA to the incubating medium. In sum, DPA has complex effects on neuronal membranes. Some of these effects may serve to explain the anticonvulsant actions of this drug.

Afferent Pathways↗
PubMed1980

Hyperpolarization of frog primary afferent fibres caused by activation of a sodium pump.

1. In the isolated frog spinal cord repetitive stimulation of a lumbar dorsal root produced a sustained negative potential recorded from an adjacent inactive dorsal root by sucrose gap techniques. This negative potential was followed by a positive potential, an indication that the dorsal root terminals were hyperpolarized. Increasing the duration of the tetanus applied to the active root increased the amplitude and duration of the after-hyperpolarization which could be up to 6 mV and 3 min respectively. 2. The hyperpolarization presumably reflected an increased rate of active sodium pumping. Since it was reversibly reduced by metabolic inhibitors (dinitrophenol, NaCN) and cooling (Q10, 2 . 6) it was clearly dependent upon intact metabolic activity. In addition, a variety of procedures used to inhibit sodium pumps (including application of ouabain, elimination of potassium from the superfusate, and partial substitution of lithium for sodium ions) significantly and reversibly decreased the potential. 3. The hyperpolarization was not dependent upon intact chemical synaptic transmission since it could survive prolonged immersion of the cord in Ringer solution containing manganese or magnesium ions. 4. It is suggested that the hyperpolarization of inactive fibres resulted from a decreased extracellular potassium concentration in the dorsal horn produced as a result of a pumping mechanism which extruded sodium and transported potassium inwards by dorsal root fibres directly activated by the tetanus.

Animals↗
PubMed1979

gamma-Hydroxybutyric acid is not a GABA-mimetic agent in the spinal cord.

gamma-Hydroxybutyric acid (GHB), a pharmacologically active central nervous system constituent, has been postulated to function as a gamma-aminobutyric acid (GABA) agonist. This hypothesis was tested directly on GABAergic synapses in isolated, superfused frog spinal cord. Addition of GHB to the superfusate produced effects on primary afferent terminals that were distinctly different from the effects of GABA. Thus, although both compounds depressed dorsal root potentials, GHB hyperpolarized terminals while GABA depolarized the same structures. The GABA responses were antagonized by bicuculline and picrotoxin, but these alkaloids did not change GHB's actions. In addition, GHB altered neither high-affinity uptake by cord slices, nor potassium-evoked release of tritiated GABA from them. GHB did not directly release GABA from spinal slices preloaded with [3H]GABA. These observations suggest that the central nervous system actions of GHB are not dependent upon its ability to activate GABAergic synapses or to modify GABAergic mechanisms.

Animals↗
PubMed1978

Some actions of catechol on synaptic transmission in the isolated spinal cord of the frog.

The isolated frog spinal cord was used to investigate the synaptic effects of the convulsant agent catechol. Addition of the compound to the superfusate consistently enhanced orthodromic reflex activity recorded from ventral roots and augmented primary afferent depolarization. Concomitantly catechol altered the polarization changes produced in ventral and dorsal roots by putative neurotransmitter amino acids when these compounds were applied in Mg2+-containing Ringer. Catechol reduced the hyperpolarizations induced in motoneurons by the neutral amino acids, GABA, beta-alanine, taurine and glycine, but did not affect the depolarizations produced by the dicarboxylic amino acids, L-glutamate and L-aspartate. In contrast, catechol increased the dorsal root depolarizations elicited by both neutral and dicarboxylic amino acids and also the depolarizations produced by elevated potassium concentrations. Catechol did not bring about significant changes in the passive electrical properties of motoneurons or dorsal root fibers. In addition, it did not alter either the high affinity uptake or the depolarization-evoked release of tritiated GABA, glycine, L-glutamate and L-aspartate. It appears that the postsynaptic actions of catechol explain its ability to enhance spinal reflexes.

Action Potentials↗
PubMed1978

Pentylenetetrazol and reflex activity of isolated frog spinal cord.

The superfused in vitro frog spinal cord preparation was used to investigate the effects of pentylenetetrazol (PTZ) on the spinal cord. PTZ depressed monosynaptic, but augmented polysynaptic reflexes, and decreased primary afferent deplorization. Concurrently, in Ringer's solution containing sufficient magnesium or cobalt ions to block synaptic transmission, PTZ antagonized the hyperpolarizing effects on motoneurons and the depolarizing effects on primary afferent fibers of the inhibitory amino acids GABA, beta-alanine, taurine, and glycine. PTZ did not affect responses to the excitatory amino acids glutamic acid and aspartic acid. Furthermore, PTZ did not alter high affinity uptake by cord slices, K+ -evoked release of [3H]GABA from them, or the spinal concentration of GABA. These data suggest that PTZ may produce its excitatory effects by postsynaptic blockade of inhibitory processes mediated by GABA (and possibly by other amino acids).

Amino Acids↗