Adjacent Dorsal Root Research Articles

The pharmacology of dorsal root potentials recorded from the isolated spinal cord of the neonate rat

1. 1. Dorsal root potentials (DRP) evoked by stimulating an adjacent dorsal root or the dorsal columns were recorded from the hemisected cord of 5–10 day old rats. 2. 2. GABA (10 −4 M) evoked a depolarization of the primary afferents and at concentrations of 10 −6, 10 −5 and 10 −4 M reduced DRP amplitude by 14, 39 and 45%, respectively. 3. 3. Bicuculline and picrotoxin (10 −5 M) reduced DRP amplitude by 62 and 52%, respectively. 4. 4. 5-HT (10 −6, 10 −5) and 10 −4 M) reduced DRP amplitude by 19, 40 and 44%, respectively. 5. 5. Phentolamine (10 −6 M) did not alter this action of 5-HT significantly, but quipazine (10 −6 M) almost entirely blocked it. 6. 6. Noradrenaline (NA) (10 −6 M) enhanced the amplitude of the DRP in some preparations and reduced it in others. Both actions were blocked by phentolamine (10 −6 M). Quipazine did not alter the effects produced by this concentration of NA. 7. 7. At higher concentrations (10 −5, 10 −4 M NA) only depressions of DRP amplitude were observed, but these effects were insensitive to phentolamine (10 −6 M). Quipazine potentiated the depressant action of NA (10 −5 M). 8. 8. DRPs were also reduced in amplitude by changes in [K +] 0. An increase to 6 or 4.5 mM reduced amplitude by 39 or 13%, respectively, while a decrease to 1.5 mM reduced it by 15%. Alteration in [K +] 0 produced changes in primary afferent resting potential. DRPs were abolished when [Cl −] 0 was reduced by 94%. 9. 9. The results are consistent with a dependence of the DRP on interneurones releasing GABA. 10. 10. Some part of the neural mechanism generating the DRP appears to possess distinct 5-HT receptors, capable of being blocked by quipazine, and α adrenoceptors; the neural mechanism is also sensitive to changes in [Cl −] 0 and [K +] 0.

Dorsal root potentials and changes in extracellular potassium in the spinal cord of the frog.

1. In the present study changes in extracellular potassium, ([K]e), were recorded in the isolated spinal cord of the frog with glial cell recordings and K-selective micro-electrodes to test the hypothesis that elevations in [K]e during neuronal activity produce the dorsal root potential (d.r.p.). 2. Sucrose gap recording from the dorsal root (d.r.) was used to record responses to root stimulation and to exogenously applied K+. 3. Stimulation of the ventral root, which elicits a d.r.p. in the frog spinal cord, was not associated with any change in [K]e, suggesting that d.r.p.s produced by ventral root stimulation are not due to changes in [K]e. 4. The largest change in [K]e observed following single stimuli to the dorsal root was 0.4 mM. Such a change in [K]e, if evenly distributed, would depolarize the dorsal root by about 1 mV and yet the simultaneously recorded d.r.p. evoked by stimulating an adjacent dorsal root (d.r.-d.r.p.) was over 10 mV. 5. The time-to-peak of the glidal cell responses was 10 times that of the d.r.-d.r.p. Low frequency (1-10 Hz) d.r. stimulation caused a decremental summation of glial cell responses, while there was no summation in the d.r.-d.r.p. These results suggest that the d.r.p. produced by single d.r. stimulation is generated in large part by a mechanism other than a change in [K]e. 6. During high frequency d.r. stimulation, which evoked 6-8 mM increases in [K]e, the adjacent d.r. was depolarized to a greater extent than that produced by single stimuli. The magnitude of this depolarization was similar to that produced by applying a [K]e equivalent to that observed in the spinal cord during high frequency stimulation. Thus, a substantial component of the sustained d.r. depolarization during high frequency d.r. stimulation may result from changes in [K]e. 7. In the presence of magnesium, high frequency d.r. stimulation evoked a picrotoxin resistant depolarization of an adjacent d.r. whose magnitude correlated well with the changes in [K]e recorded in the spinal cord. 8. In the presence of picrotoxin a slow, long duration depolarization of the d.r. occurred following single stimuli to the adjacent d.r. and the appearance and time course of this response correlated well with the time course of changes in [K]e. 9. Addition of K+ to the Ringer solution in concentrations up to 12 mM had a facilitatory action on reflex activity in the frog spinal cord. 10 The present results suggest that although changes in [K]e play a relatively minor role in generating d.r.p.s. elicited by single d.r. stimulation, the sustained dorsal root depolarization evoked either by high frequency stimulation or by single stimuli in the presence of picrotoxin may be due to a considerable extent to [K]e.

The interaction of four putative glutamate antagonists with glutamate and their effects on the toad spinal cord

1. 1. Four putative glutamate antagonists ( l-glutamate diethyl ester, l-glutamate dimethyl ester, l-proline and 1-hydroxy-3-amino-pyrrolidone-2) were tested on the isolated hemisected toad spinal cord. 2. 2. 1-hydroxy-3-amino-pyrrolidone-2 (10 −3–10 −2 M) selectively antagonized the depolarizations evoked in both dorsal and ventral roots by applications of l-glutamate (5 × 10 −4 M). 3. 3. 1-hydroxy-3-amino-pyrrolidone-2 also antagonized the depolarizations evoked in both dorsal and ventral roots by stimulation of the adjacent dorsal root. 4. 4. The dimethyl and diethyl esters of l-glutamate and l-proline had their own depolarizing actions on the dorsal and ventral roots, and neither potentiated nor antagonized the effects of l-glutamate. 5. 5. The results with 1-hydroxy-3-amino-pyrrolidone-2 offer further evidence for the involvement of l-glutamate and l-aspartate in synaptic transmission in the amphibian spinal cord.

Pentylenetetrazol: An antagonist of gaba at primary afferents of the isolated frog spinal cord

In the isolated frog spinal cord, pentylenetetrazole in concentrations over 10 −2 M, selectively abolished dorsal root potential evoked by ventral root stimulation and attenuated dorsal root potential generated by stimulation of adjacent dorsal root. In the same concentration pentylenetetrazole differentially affected some neutral amino acid responses without interfering with the glutamate response. On the dorsal root, β-alanine and taurine depolarizing responses were abolished and the γ-aminobutyric acid response was attenuated. In contrast to other convulsants, pentylenetetrazole was found to antagonize the depolarizing component of neutral amino acid responses of frog motoneurones.

Studies on convulsants in the isolated frog spinal cord. II. Effects on root potentials.

1. In the isolated frog spinal cord picrotoxin, bicuculline, and strychnine were evaluated for their effects on synaptically induced root potentials recorded by the sucrose gap technique. 2. Picrotoxin (greater than 10- minus 4 M) completely blocked the dorsal root potential (DRP) elicited by stimulating the ventral root of the same segment (VR-DRP). Although picrotoxin antagonized the DRP elicited by stimulation of either an adjacent dorsal root (DR-DRP) or the lateral column (LC-DRP), a slower component to these potentials appeared and increased in size as the concentration of picrotoxin was increased. Thus picrotoxin brings out a later, picrotoxin resistant component to the DR-DRP and LC-DRP. 3. Strychnine (10- minus 8-10- minus 5 M) reduced and abolished the VR-DRP without prolongation and progressively increased and prolonged the DR-DRP (and LC-DRP) and the DR-VRP. Strychnine in higher concentrations (greater than 10- minus 4 M) also reduced the amplitude and prolonged the duration of the compound action potential of afferent fibres. 4. These results combined with those presented in the preceding paper (Barker, Nicoll & Padjen, 1975) suggest that (1) a GABA-like transmitter mediates the final step in the DR-DRP and LC-DRP pathways and that (2) either taurine or beta-alanine may mediate the last step in the VR-DRP pathway.

Bicuculline and the frog spinal cord.

1 The effects of bicuculline on dorsal and ventral root activity and upon the depressant effect of gamma-aminobutyric acid (GABA) and glycine on ventral root responses have been studied on the isolated spinal cord of the frog.2 In the absence of stimulation, the alkaloid induced a variety of activity of which the most notable was phasic simultaneous slow wave depolarization in the dorsal and ventral roots which could be reduced or suppressed by magnesium.3 With low concentrations of bicuculline, the adjacent dorsal root response evoked by a single stimulus was depressed maximally before an increase in the ventral root response could be discerned.4 The bicuculline-induced dorsal root activity (in the absence of stimulation) was still apparent at times when the evoked dorsal root response was reduced.5 Bicuculline did not differentiate between the depressant effects of GABA and glycine on the evoked ventral root responses.6 The excitant effects of bicuculline reported here did not appear to be attributable to specific antagonism of the postsynaptic depressant action of GABA.

Centrifugal dorsal root discharges induced by motoneurone activation.

1. It has been confirmed that antidromic stimulation of motoneurones in the cat lumbar cord can induce, when properly conditioned, a centrifugal discharge in dorsal root afferent fibres.2. The effective conditioning can be (a) an orthodromic volley to the same or an adjacent dorsal root, (b) a volley to the dorsal column one or two segments above the tested level, or (c) a natural stimulus applied to the ipsi- or contralateral hind limb.3. The conditioning stimulus acts by increasing presynaptic excitability; the peak of its effect (maximum presynaptic depolarization) occurs 7-10 msec after the arrival of the conditioning volley to the cord and then quickly decays.4. A large antidromic field potential in the ventral horn is not necessary for the production of a centrifugal dorsal root discharge. Activation of a ventral root filament of approximately 100 mu in diameter can still induce such a discharge in a single dorsal root fibre. Furthermore, antidromic stimulation of the remaining fibres of the same ventral root cannot affect the terminals activated by the thin ventral root filament.5. The phenomenon of motoneurone-presynaptic interaction was obtained in different types of experimental preparations: acute and chronic spinal, anaemic and midcollicular decerebrate, animals with intact supraspinal centres, and one animal without acute laminectomy.

Action of some drugs on the dorsal root potentials of the isolated toad spinal cord.

A series of drugs which potentiate or antagonize transmission at cholinergic synapses have been tested on the slow depolarizing dorsal root potentials evoked by stimulation of adjacent dorsal and ventral roots. Some drugs acted specifically on the dorsal root potential evoked by ventral root stimulation. Dihydro-beta-erythroidine, atropine and acetylcholine depressed this potential, whilst anticholinesterase substances in low concentrations potentiated and in higher concentrations depressed it. It is concluded that the results offer some evidence for a cholinergic link in the pathway responsible for the generation of depolarizing potentials in the dorsal root subsequent to ventral root stimulation.

Pharmacological behavior of spinal cord potentials relative to reflex and ascending discharge.

The slow negative and positive potentials recorded at the cord dorsum and at an adjacent dorsal root in response to a dorsal root volley were relatively insensitive to mephenesin, morphine, Dial, Nembutal, chloralose, eserine, amyl carbamate and, less clearly, urethane. In the doses used, mephenesin (and, to a lesser extent, morphine) markedly depressed the longer-latency, polysynaptic components of the reflex discharge and of the ascending tract responses in the contraventrolateral and ipsidorsolateral columns. The other drugs affected the monosynaptic reflex as much as or more than the polysynaptic discharge. The carbamates used depressed the monosynaptic reflex in smaller doses with increasing length of the aliphatic chain. The lack of parallelism between behavior of the slow cord potentials and the reflex or ascending discharge is explainable by the hypothesis that the slow potentials result from graded postsynaptic potentials in certain groups of interneurons. The insensitivity to eserine suggests that such postsynaptic potentials are developed at noncholinergic junctions.