Extrasynaptic effects of GABA (γ-aminobutyric acid) agonists on myelinated axons of peripheral nerve

1994 ◽  
Vol 72 (4) ◽  
pp. 368-374 ◽  
Author(s):  
S. Liske ◽  
M. E. Morris
Keyword(s):  
Peripheral Nerve ◽  
Recovery Phase ◽  
Ventral Root ◽  
Aminobutyric Acid ◽  
Myelinated Axons ◽  
Bicuculline Methiodide ◽  
Proximal Site ◽  
Spinal Roots ◽  
Sciatic Nerves ◽  
Ventral Roots

Effects of the inhibitory neurotransmitter, GABA (γ-aminobutyric acid) on the excitability of myelinated fibers of isolated amphibian sciatic nerves and their dorsal and ventral spinal roots have been compared with those of a GABAA agonist, THIP (4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol), and the GABAB agonist baclofen. Graded, prolonged increases in the amplitude of A-fiber half-maximal compound action potentials of Rana ballenderi sciatic nerves were evoked by GABA (Rmax = 49%, EC50 = 0.1 mM); responses to THIP were smaller (Rmax = 34%, EC50 = 1.1 mM) and with a different, distinctly biphasic recovery phase. In studies of Rana catesbeiana nerves and their attached spinal roots, excitability increases produced in fibers of the ventral roots by GABA were smaller than those of the dorsal roots. Peak changes evoked by THIP in both roots were similar to the effects of GABA on the ventral root; however, THIP's ventral root response showed much less sensitivity and was followed by a rapid recovery phase, undershoot, and secondary, prolonged enhancement. Bicuculline methiodide antagonized agonist-induced increases, and revealed the presence of significant decreases in excitability of the ventral root fibers at concentrations of GABA or THIP < 3 mM. Baclofen evoked inconsistent changes in the excitability of whole nerve and root fibers; small increases occurred with lower doses and secondary, delayed decreases with higher doses. The high concentration (≥ 0.1 mM) of the active isomer needed to cause a small response suggests a limited contribution and (or) presence of GABAB receptors. GABA and its agonists evoke complex, multiphasic excitability changes in the myelinated axons of the spinal roots and peripheral nerve. Contributions of different phases of increase and directions of change signify the participation of multiple receptors and (or) mechanisms. Responses of the dorsal root appear to reflect mainly GABAA-mediated increases in excitability; those of the ventral root include an additional or greater decrease, which may reflect a hyperpolarizing component mediated by a GABAC-like or bicuculline methiodide insensitive GABAA receptor. The large, prolonged responses of the sensory axons to GABA may be linked to their greater K+ channel conductance and related to the inhibitory transmitter's depolarizing action at the more proximal site of their central presynaptic terminals.Key words: dorsal and ventral roots, amphibian, excitability, GABAA, GABAB, GABAC.

Effects of GABA, THIP, and potassium on excitability of myelinated axons of isolated amphibian spinal roots

1989 ◽  
Vol 67 (6) ◽  
pp. 682-685 ◽  
Author(s):  
S. Liske ◽  
M. E. Morris
Keyword(s):  
Action Potentials ◽  
Dorsal Root ◽  
Ventral Root ◽  
Aminobutyric Acid ◽  
Nerve Bundle ◽  
Myelinated Axons ◽  
Root Sheath ◽  
Compound Action Potentials ◽  
Spinal Roots ◽  
Compound Action

The effects of direct applications of GABA (γ-aminobutyric acid) and the GABAA agonist, THIP (4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol) on the excitability of myelinated axons of individual dorsal and ventral spinal roots (lumbar VI and (or) VII) of the isolated bullfrog peripheral nerve are reported. Increases evoked by the GABA agonists (0.01–10 mM) in the amplitude of half-maximal A-fiber compound action potentials indicate the presence of depolarizing responses with apparently greater localization to the dorsal roots, and a sensitivity to GABA twofold greater than that for THIP. The changes evoked by GABA and THIP, as well as potassium have components that closely resemble those of sensory and motor fibers in the more distal, desheathed nerve bundle but are smaller and delayed, differences attributable to a closely attached root sheath that acts as a diffusion barrier. These results confirm the likely existence of GABAA receptors on both dorsal and ventral spinal roots.Key words: GABAA receptors, dorsal root fibers, ventral root fibers, depolarization, hyperpolarization.

Organization of peripheral nerves and spinal roots of the Atlantic stingray, Dasyatis sabina

1978 ◽  
Vol 41 (1) ◽  
pp. 97-107 ◽  
Author(s):  
R. E. Coggeshall ◽  
R. B. Leonard ◽  
M. L. Applebaum ◽  
W. D. Willis
Keyword(s):  
Dorsal Root Ganglion ◽  
Peripheral Nerves ◽  
Dorsal Root ◽  
Ganglion Cells ◽  
Ventral Root ◽  
Dasyatis Sabina ◽  
Unmyelinated Axons ◽  
Spinal Roots ◽  
Ventral Roots ◽  
Dorsal Root Ganglion Cells

1. The sizes and numbers of axons in peripheral nerves and spinal roots were investigated in the stingray, Dasyatis sabina. 2. The axons of the dorsal and ventral roots do not mingle in peripheral nerves of this animal as they do in higher vertebrates. Thus, it was usually possible to split the peripheral nerve into two portions, one containing only dorsal root axons, the other containing only ventral root axons. This feature was useful for the analysis of certain aspects of spinal cord organization. 3. The fact that dorsal and ventral root axons were segregated in peripheral nerves enabled us to demonstrate, without experimental surgery, that the central processes of the dorsal root ganglion cells and the proximal ventral root axons were 10-20% narrower, on the average, than the distal processes of the same dorsal root ganglion cells or the distal parts of the same ventral root axons. 4. The stingray is remarkable in having very few unmyelinated axons in the dorsal roots, ventral roots, or peripheral nerves. This paucity of unmyelinated axons distinguishes the Atlantic stingrays from all other vertebrates whose roots and nerves have been examined for unmyelinated fibers. 5. Similar findings were obtained for one spotted eagle ray (Aetobatus narinari) and two cow-nose rays (Rhinoptera bonasus).

Comparison of changes evoked by GABA (γ-aminobutyric acid) and anoxia in [K+]o, [Cl-]o, and [Na+]o in stratum pyramidale and stratum radiatum of the guinea pig hippocampus

2000 ◽  
Vol 78 (5) ◽  
pp. 378-391 ◽  
Author(s):  
G V Obrocea ◽  
M E Morris
Keyword(s):  
Guinea Pig ◽  
Extracellular Space ◽  
Hippocampal Slices ◽  
Brain Slices ◽  
Receptor Activation ◽  
Ion Concentration ◽  
Aminobutyric Acid ◽  
Stratum Radiatum ◽  
Bicuculline Methiodide ◽  
Stratum Pyramidale

Ion-selective microelectrode recordings were made to assess a possible contribution of extracellular γ-aminobutyric acid (GABA) accumulation to early responses evoked in the brain by anoxia and ischemia. Changes evoked by GABA or N2 in [K+]o, [Cl-]o, [Na+]o, and [TMA+]o were recorded in the cell body and dendritic regions of the stratum pyramidale (SP) and stratum radiatum (SR), respectively, of pyramidal neurons in CA1 of guinea pig hippocampal slices. Bath application of GABA (1-10 mM) for approximately 5 min evoked changes in [K+]o and [Cl-]o with respective EC50 levels of 3.8 and 4.1 mM in SP, and 4.7 and 5.6 mM in SR. In SP 5 mM GABA reversibly increased [K+]o and [Cl-]o and decreased [Na+]o; replacement of 95% O2 -5% CO2 by 95% N2 -5% CO2 for a similar period of time evoked changes which were for each ion in the same direction as those with GABA. In SR both GABA and N2 caused increases in [K+]o and decreases in [Cl-]o and [Na+]o. The reduction of extracellular space, estimated from levels of [TMA+]o during exposures to GABA and N2, was 5-6% and insufficient to cause the observed changes in ion concentration. Ion changes induced by GABA and N2 were reversibly attenuated by the GABAA receptor antagonist bicuculline methiodide (BMI, 100 µM). GABA-evoked changes in [K+]o in SP and SR and [Cl-]o in SP were depressed by >=90%, and of [Cl-]o in SR by 50%; N2-evoked changes in [K+]o in SP and SR were decreased by 70% and those of [Cl-]o by 50%. BMI blocked Δ [Na+]o with both GABA and N2 by 20-30%. It is concluded that during early anoxia: (i) accumulation of GABA and activation of GABAA receptors may contribute to the ion changes and play a significant role, and (ii) responses in the dendritic (SR) regions are greater than and (or) differ from those in the somal (SP) layers. A large component of the [K+]o increase may involve a GABA-evoked Ca2+-activated gk, secondary to [Ca2+]i increase. A major part of [Cl-]o changes may arise from GABA-induced gCl and glial efflux, with strong stimulation of active outward transport and anion exchange at SP, and inward Na+/K+/2Cl- co-transport at SR. Na+ influx is attributable mainly to Na+-dependent transmitter uptake, with only a small amount related to GABAA receptor activation. Although the release and (or) accumulation of GABA during anoxia might be viewed as potentially protectant, the ultimate role may more likely be an important contribution to toxicity and delayed neuronal death. Key words: brain slices, ion-selective microelectrodes, stratum pyramidale, stratum radiatum, bicuculline methiodide, extracellular space shrinkage.

Transplantation of Schwann cells in a collagen tube for the repair of large, segmental peripheral nerve defects in rats

2013 ◽  
Vol 119 (3) ◽  
pp. 720-732 ◽  
Author(s):  
Yerko A. Berrocal ◽  
Vania W. Almeida ◽  
Ranjan Gupta ◽  
Allan D. Levi
Keyword(s):  
Sciatic Nerve ◽  
Peripheral Nerve ◽  
Schwann Cells ◽  
Nerve Injury ◽  
Peripheral Nerve Injury ◽  
Fluorescent Protein ◽  
Control Groups ◽  
Myelinated Axons ◽  
Segmental Nerve ◽  
Green Fluorescent

Object Segmental nerve defects pose a daunting clinical challenge, as peripheral nerve injury studies have established that there is a critical nerve gap length for which the distance cannot be successfully bridged with current techniques. Construction of a neural prosthesis filled with Schwann cells (SCs) could provide an alternative treatment to successfully repair these long segmental gaps in the peripheral nervous system. The object of this study was to evaluate the ability of autologous SCs to increase the length at which segmental nerve defects can be bridged using a collagen tube. Methods The authors studied the use of absorbable collagen conduits in combination with autologous SCs (200,000 cells/μl) to promote axonal growth across a critical size defect (13 mm) in the sciatic nerve of male Fischer rats. Control groups were treated with serum only–filled conduits of reversed sciatic nerve autografts. Animals were assessed for survival of the transplanted SCs as well as the quantity of myelinated axons in the proximal, middle, and distal portions of the channel. Results Schwann cell survival was confirmed at 4 and 16 weeks postsurgery by the presence of prelabeled green fluorescent protein–positive SCs within the regenerated cable. The addition of SCs to the nerve guide significantly enhanced the regeneration of myelinated axons from the nerve stump into the proximal (p < 0.001) and middle points (p < 0.01) of the tube at 4 weeks. The regeneration of myelinated axons at 16 weeks was significantly enhanced throughout the entire length of the nerve guide (p < 0.001) as compared with their number in a serum–only filled tube and was similar in number compared with the reversed autograft. Autotomy scores were significantly lower in the animals whose sciatic nerve was repaired with a collagen conduit either without (p < 0.01) or with SCs (p < 0.001) when compared with a reversed autograft. Conclusions The technique of adding SCs to a guidance channel significantly enhanced the gap distance that can be repaired after peripheral nerve injury with long segmental defects and holds promise in humans. Most importantly, this study represents some of the first essential steps in bringing autologous SC-based therapies to the domain of peripheral nerve injuries with long segmental defects.

Unmyelinated and small myelinated axons in rat ventral roots

1977 ◽  
Vol 173 (1) ◽  
pp. 175-184 ◽  
Author(s):  
Richard E. Coggeshall ◽  
Dennis G. Emery ◽  
Haruhide Ito ◽  
Christine W. Maynard
Keyword(s):  
Myelinated Axons ◽  
Ventral Roots

ATP concentrations and muscle tension increase linearly with muscle contraction

2003 ◽  
Vol 95 (2) ◽  
pp. 577-583 ◽  
Author(s):  
Jianhua Li ◽  
Nicholas C. King ◽  
Lawrence I. Sinoway
Keyword(s):  
Skeletal Muscle ◽  
Electrical Stimulation ◽  
Muscle Contraction ◽  
Motor Nerve ◽  
Muscle Tension ◽  
Nerve Fibers ◽  
Ventral Root ◽  
Ventral Roots ◽  
Root Stimulation ◽  
Stimulation Of

Previous studies have suggested that activation of ATP-sensitive P2X receptors in skeletal muscle play a role in mediating the exercise pressor reflex (Li J and Sinoway LI. Am J Physiol Heart Circ Physiol 283: H2636–H2643, 2002). To determine the role ATP plays in this reflex, it is necessary to examine whether muscle interstitial ATP (ATPi) concentrations rise with muscle contraction. Accordingly, in this study, muscle contraction was evoked by electrical stimulation of the L7 and S1 ventral roots of the spinal cord in 12 decerebrate cats. Muscle ATPi was collected from microdialysis probes inserted in the muscle. ATP concentrations were determined by the HPLC method. Electrical stimulation of the ventral roots at 3 and 5 Hz increased mean arterial pressure by 13 ± 2 and 16 ± 3 mmHg ( P < 0.05), respectively, and it increased ATP concentration in contracting muscle by 150% ( P < 0.05) and 200% ( P < 0.05), respectively. ATP measured in the opposite control limb did not rise with ventral root stimulation. Section of the L7 and S1 dorsal roots did not affect the ATPi seen with 5-Hz ventral root stimulation. Finally, ventral roots stimulation sufficient to drive motor nerve fibers did not increase ATP in previously paralyzed cats. Thus ATPi is not largely released from sympathetic or motor nerves and does not require an intact afferent reflex pathway. We conclude that ATPi is due to the release of ATP from contracting skeletal muscle cells.

scholarly journals The dynamic changes of main cell types in the microenvironment of sciatic nerves following sciatic nerve injury and the influence of let-7 on their distribution

RSC Advances ◽  
2018 ◽  
Vol 8 (72) ◽  
pp. 41181-41191 ◽  
Author(s):  
Tianmei Qian ◽  
Pan Wang ◽  
Qianqian Chen ◽  
Sheng Yi ◽  
Qianyan Liu ◽  
...  
Keyword(s):  
Sciatic Nerve ◽  
Peripheral Nerve ◽  
Schwann Cells ◽  
Nerve Injury ◽  
Cell Types ◽  
Sciatic Nerve Injury ◽  
Dynamic Changes ◽  
Main Cell ◽  
Sciatic Nerves

Schwann cells (SCs), fibroblasts and macrophages are the main cells in the peripheral nerve stumps.

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