Pharmacology of isolated mammalian spinal cord
Pharmacology of isolated mammalian spinal cord
The aim of this work was to develop the use of a mammalian in vitro spinal cord preparation from young hamsters as a model for studying the pharmacological properties of the spontaneous activity in dorsal and ventral roots and the electrophysiological and pharmacological properties of the spinal inhibition. The spontaneous activity in dorsal roots was increased by exposure to aminopyridines (APs). The order of potency for the tested aminopyridines was: 3,4-DAP> 4-AP> 3-AP = 2,3-DAP = 2-AP> 2,6-DAP. The maximum effective concentration of each drug was: 4-AP at 3 x 10-5M; 3-AP at 10-3M; 2-AP at 10-3M; 3,4-DAP at 10-4M; 2,3-DAP at 10-3M and 2,6-DAP at 3 x 10-3M. Similar results were also seen in ventral roots; but while the activity in dorsal roots returned to normal firing when the APs were washed off, the activity in ventral roots ceased for a period of time. The sensitivity of the spontaneous activity in ventral and dorsal roots to APs indicates that K+-channels may be involved in this activity. The frequency of spontaneous activity in the ventral roots was increased by 5-hydroxytryptamine (5-HT) dopamine (DA), decamethonium and d-tubo-curarine and inhibited by nicotine while the activity in dorsal roots was inhibited by 5-HT, DA and decamethonium. Stimulation of the lumbar dorsal roots evoked synchrynous short latency compound action potentials in the ventral root, which were presumed to be monosynaptically generated, and a long latency, asynchrynous burst of action potentials probably polysynaptic in origin. The effect of spinal inhibition on both the spontaneous and evoked activity in the ventral roots has been studied. Repetitive antidromic stimuli applied to ventral roots reduced the spontaneous activity in the adjacent ventral root by approximately 25% for up to 100 ms. Conditioning stimuli applied to the lateral side of the spinal cord produced intense inhibition of both spontaneous and evoked ventral root activity. At a stimulus strength of 20V the dorsal root-ventral root reflex was reduced to 95% of the control activity. This period of inhibition lasted approximately 80 ms, and was followed by an increase in activity above that recorded in the control. Studies on the time course of inhibition showed that the maximal inhibition was at a C-T interval of 20-100 ms. 3 x 10-5M of d-tubocurarine and strychnine reduced the inhibition caused by the conditioning stimulus. The largest effect was observed at 20-200 ms. This might indicate the involvement of cholinergic and glycine synaptic transmission in this inhibition, and the possibility of an involvement of Renshaw cells is discussed.
University of Southampton
Al-Zamil, Zeid Muhammed Zeid
1989
Al-Zamil, Zeid Muhammed Zeid
Al-Zamil, Zeid Muhammed Zeid
(1989)
Pharmacology of isolated mammalian spinal cord.
University of Southampton, Doctoral Thesis.
Record type:
Thesis
(Doctoral)
Abstract
The aim of this work was to develop the use of a mammalian in vitro spinal cord preparation from young hamsters as a model for studying the pharmacological properties of the spontaneous activity in dorsal and ventral roots and the electrophysiological and pharmacological properties of the spinal inhibition. The spontaneous activity in dorsal roots was increased by exposure to aminopyridines (APs). The order of potency for the tested aminopyridines was: 3,4-DAP> 4-AP> 3-AP = 2,3-DAP = 2-AP> 2,6-DAP. The maximum effective concentration of each drug was: 4-AP at 3 x 10-5M; 3-AP at 10-3M; 2-AP at 10-3M; 3,4-DAP at 10-4M; 2,3-DAP at 10-3M and 2,6-DAP at 3 x 10-3M. Similar results were also seen in ventral roots; but while the activity in dorsal roots returned to normal firing when the APs were washed off, the activity in ventral roots ceased for a period of time. The sensitivity of the spontaneous activity in ventral and dorsal roots to APs indicates that K+-channels may be involved in this activity. The frequency of spontaneous activity in the ventral roots was increased by 5-hydroxytryptamine (5-HT) dopamine (DA), decamethonium and d-tubo-curarine and inhibited by nicotine while the activity in dorsal roots was inhibited by 5-HT, DA and decamethonium. Stimulation of the lumbar dorsal roots evoked synchrynous short latency compound action potentials in the ventral root, which were presumed to be monosynaptically generated, and a long latency, asynchrynous burst of action potentials probably polysynaptic in origin. The effect of spinal inhibition on both the spontaneous and evoked activity in the ventral roots has been studied. Repetitive antidromic stimuli applied to ventral roots reduced the spontaneous activity in the adjacent ventral root by approximately 25% for up to 100 ms. Conditioning stimuli applied to the lateral side of the spinal cord produced intense inhibition of both spontaneous and evoked ventral root activity. At a stimulus strength of 20V the dorsal root-ventral root reflex was reduced to 95% of the control activity. This period of inhibition lasted approximately 80 ms, and was followed by an increase in activity above that recorded in the control. Studies on the time course of inhibition showed that the maximal inhibition was at a C-T interval of 20-100 ms. 3 x 10-5M of d-tubocurarine and strychnine reduced the inhibition caused by the conditioning stimulus. The largest effect was observed at 20-200 ms. This might indicate the involvement of cholinergic and glycine synaptic transmission in this inhibition, and the possibility of an involvement of Renshaw cells is discussed.
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Published date: 1989
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Local EPrints ID: 462694
URI: http://eprints.soton.ac.uk/id/eprint/462694
PURE UUID: ba57f39c-e066-4c44-8a52-6961bec6ee54
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Date deposited: 04 Jul 2022 19:41
Last modified: 04 Jul 2022 19:41
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Author:
Zeid Muhammed Zeid Al-Zamil
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