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Substance P selectively blocks excitation of Renshaw cell by acetylcholine Depurfr??entof Ancresthesia Research, McGilB University, Montreal, P.Q., Canada H3G I Y 6 Received June 1 4, I977 KRNJEVI~, K., and L E K I ~D. , 1977. Substance P selectively blocks excitation of Renshaw cell by acetylcholine. Can. J. Physiol. Pharmacol. 55, 958-961. In cats, under Dial anaesthesia, Renshaw cells were excited by microiontc~phoretic applications of acetylcholine (ACh), aspartate, and glutamate. Substance P, in small doses (10-30 nA), selectively abolished the responses to ACh, leaving the discharges evoked by the amino acids unchanged or enhanced. Higher doses ( >50 nA) depressed all responses, but those evoked by amino acids went down last and recovered sooner. By contrast, neither synaptic responses to ventral root stimulation nor spontaneous discharges were affected by substance P, presun~ablyowing to the high efficacy of synaptic transmission and the presence of diffusion harriers around junctional sites. KRNJEVI~, K. et I,EKI~,D. 1977. Substance P selectively blocks excitation of Renshaw cell by acetylcholine. Can. J. Physiol. Pharrnacol. 55, 958-961. Chez dcs chats, anestbCsiCs au Dial, les cellules Renshaw sont excitCes par applications microiontophorCtiques d'acetylcholine (ACh), d'aspartate et de glutamate. IInjectCe par de faibles courants (10-30 nA), la substance P inhibe de manikre sClcctive les rkponses B I'ACh alors que Ies rCponses aux acides aminks persistent ou sont mime augrnentkes. Des injections plus importantes de substance B dkpriment toutes Bes r$ponses, mais les iiCcharges 12voquCcs par les acidcs anlinks persistent plus longtcmps et ric~tpkrentplus t8t. A l'encontrc des dkcharges induites par microiontcpphorkse, les ~Cponsessynaptiques B la stimulation des racines ve~mtrales,ainsi que les dCcharges spontankes, sont trks resistantes aux effets de la substance P, sans doute A cause de la grande eficacitk cle ces synapses, et aussi peut-etre parce que l'accks aux rCcepteurs synaptiques est limit6 par des barrikres B la diffusion.
Introduction The predominant effect of sp on neurones in the mammalian spinal cord and medulla is a prolonged excitation ( ~ ~ and~ ~ j ~ ~r 1974; H~~~~ 1975 1. *lthough some depressant action is also detectable, this is usually associated with soitle degree of excitation. On tlae otlaer hand, Renshaw cells showed an exclusively depressant effect of sP on firing evoked with Glu (Henry eb al. 1975). In the ARRREVIATIONS: ACh, acetylcholine; Asp, aspartate; GIu. giutamatc; sP, substance P. 'Please address correspondence to: Dr. K. KrnjeviC, Department of Anaesthesia Research, McGill University, Mclntyre Medical Building, 3655 Drummond Street, Montreal, P.Q., Canada H3G BY6. 'Canada Council Fellow, on leave from the Department of Pathophysiology, University of Belgrade, Belgrade, Yugoslavia.
present experiments, Renshaw cell discharges were evoked by ACh. as well as by excitatory amino acids. When sP was also applied, it proved r ~i ~ito be ~ particularly effective in blocking the ACh-evoked firing. Comparable findings beell reported very recently by Belcher ernl. (1977).
Methods The experiments were performed on cats under Dial anaesthesia. The lumbar region of the spinal cord was exposed by a conventional laminectorny and kept under a layer of mineral oil. The cord was transsectcd at the level of the first lumbar vertebra. Five- or sevenbarrelled nnicropipettes were used to record extracellular unit spikes and to apply various agents by microiontophoresis. Thc principal substances were ACh chloride ( B M, at pH 4 ) , Na-L-Gl~aand Na-L-Asp (both 1 M, at p H near 71, and synthetic sP (Beckman Limited, 7 rnM; in 18 mM acetic acid, p H 5 . 5 ) . Renshaw cells were identified b y the characteristic high
Can. J. Physiol. Pharmacol. Downloaded from www.nrcresearchpress.com by UNIV CHICAGO on 12/26/14 For personal use only.
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959
FIG.1. Selective block of ACh-cvoked responses of Renshaw cell. Lower trace is rate-meter display of firing evoked by alternating applications of L-Asp. ACh, and I
Substance P selectively blocks excitation of Renshaw cell by acetylcholine Depurfr??entof Ancresthesia Research, McGilB University, Montreal, P.Q., Canada H3G I Y 6 Received June 1 4, I977 KRNJEVI~, K., and L E K I ~D. , 1977. Substance P selectively blocks excitation of Renshaw cell by acetylcholine. Can. J. Physiol. Pharmacol. 55, 958-961. In cats, under Dial anaesthesia, Renshaw cells were excited by microiontc~phoretic applications of acetylcholine (ACh), aspartate, and glutamate. Substance P, in small doses (10-30 nA), selectively abolished the responses to ACh, leaving the discharges evoked by the amino acids unchanged or enhanced. Higher doses ( >50 nA) depressed all responses, but those evoked by amino acids went down last and recovered sooner. By contrast, neither synaptic responses to ventral root stimulation nor spontaneous discharges were affected by substance P, presun~ablyowing to the high efficacy of synaptic transmission and the presence of diffusion harriers around junctional sites. KRNJEVI~, K. et I,EKI~,D. 1977. Substance P selectively blocks excitation of Renshaw cell by acetylcholine. Can. J. Physiol. Pharrnacol. 55, 958-961. Chez dcs chats, anestbCsiCs au Dial, les cellules Renshaw sont excitCes par applications microiontophorCtiques d'acetylcholine (ACh), d'aspartate et de glutamate. IInjectCe par de faibles courants (10-30 nA), la substance P inhibe de manikre sClcctive les rkponses B I'ACh alors que Ies rCponses aux acides aminks persistent ou sont mime augrnentkes. Des injections plus importantes de substance B dkpriment toutes Bes r$ponses, mais les iiCcharges 12voquCcs par les acidcs anlinks persistent plus longtcmps et ric~tpkrentplus t8t. A l'encontrc des dkcharges induites par microiontcpphorkse, les ~Cponsessynaptiques B la stimulation des racines ve~mtrales,ainsi que les dCcharges spontankes, sont trks resistantes aux effets de la substance P, sans doute A cause de la grande eficacitk cle ces synapses, et aussi peut-etre parce que l'accks aux rCcepteurs synaptiques est limit6 par des barrikres B la diffusion.
Introduction The predominant effect of sp on neurones in the mammalian spinal cord and medulla is a prolonged excitation ( ~ ~ and~ ~ j ~ ~r 1974; H~~~~ 1975 1. *lthough some depressant action is also detectable, this is usually associated with soitle degree of excitation. On tlae otlaer hand, Renshaw cells showed an exclusively depressant effect of sP on firing evoked with Glu (Henry eb al. 1975). In the ARRREVIATIONS: ACh, acetylcholine; Asp, aspartate; GIu. giutamatc; sP, substance P. 'Please address correspondence to: Dr. K. KrnjeviC, Department of Anaesthesia Research, McGill University, Mclntyre Medical Building, 3655 Drummond Street, Montreal, P.Q., Canada H3G BY6. 'Canada Council Fellow, on leave from the Department of Pathophysiology, University of Belgrade, Belgrade, Yugoslavia.
present experiments, Renshaw cell discharges were evoked by ACh. as well as by excitatory amino acids. When sP was also applied, it proved r ~i ~ito be ~ particularly effective in blocking the ACh-evoked firing. Comparable findings beell reported very recently by Belcher ernl. (1977).
Methods The experiments were performed on cats under Dial anaesthesia. The lumbar region of the spinal cord was exposed by a conventional laminectorny and kept under a layer of mineral oil. The cord was transsectcd at the level of the first lumbar vertebra. Five- or sevenbarrelled nnicropipettes were used to record extracellular unit spikes and to apply various agents by microiontophoresis. Thc principal substances were ACh chloride ( B M, at pH 4 ) , Na-L-Gl~aand Na-L-Asp (both 1 M, at p H near 71, and synthetic sP (Beckman Limited, 7 rnM; in 18 mM acetic acid, p H 5 . 5 ) . Renshaw cells were identified b y the characteristic high
Can. J. Physiol. Pharmacol. Downloaded from www.nrcresearchpress.com by UNIV CHICAGO on 12/26/14 For personal use only.
COMMUNICATIONS
959
FIG.1. Selective block of ACh-cvoked responses of Renshaw cell. Lower trace is rate-meter display of firing evoked by alternating applications of L-Asp. ACh, and I
