Substance P selectively blocks excitation of Renshaw cell by acetylcholine

1977 ◽  
Vol 55 (4) ◽  
pp. 958-961 ◽  
Author(s):  
K. Krnjević ◽  
Dušan Lekić
Keyword(s):  
Amino Acids ◽  
Substance P ◽  
Diffusion Barriers ◽  
Ventral Root ◽  
Renshaw Cells ◽  
Renshaw Cell ◽  
Small Doses ◽  
Higher Doses ◽  
Root Stimulation ◽  
Synaptic Responses

In cats, under Dial anaesthesia, Renshaw cells were excited by microiontophoretic 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, presumably owing to the high efficacy of synaptic transmission and the presence of diffusion barriers around junctional sites.

Influence of substance P on myoelectric activity of the small bowel

1982 ◽  
Vol 243 (6) ◽  
pp. G493-G496 ◽  
Author(s):  
P. J. Thor ◽  
R. Sendur ◽  
S. J. Konturek
Keyword(s):  
Small Bowel ◽  
Substance P ◽  
Intestinal Motility ◽  
Conscious Dogs ◽  
Myoelectric Activity ◽  
Stimulatory Action ◽  
Motility Pattern ◽  
Small Doses ◽  
Silver Electrodes ◽  
Higher Doses

The effects of substance P (SP) on intestinal myoelectric activity were examined in conscious dogs with implanted silver electrodes on the small doses (0.25-1.0 nmol . kg-1 . h-1) raised the frequency of interdigestive myoelectric complexes and also increased preburst activity, mostly in the upper small bowel. The ileum was relatively less sensitive to the stimulatory action of sp. At higher doses (2.04.0 nmol . kg-1 . h-1) SP caused a fedlike motility pattern. In the doses used SP did not change the foodinduced motility pattern. The effects of SP on myoelectric activity were blocked by atropine or pirenzepine. We conclude that SP was participate in neurally mediated changes in intestinal motility.

Histrionicotoxin: Effects on Some Central and Peripheral Excitable Cells

1974 ◽  
Vol 52 (6) ◽  
pp. 1220-1226 ◽  
Author(s):  
M. Glavinović ◽  
J. L. Henry ◽  
G. Kato ◽  
K. Krnjević ◽  
E. Puil
Keyword(s):  
Mechanism Of Action ◽  
Ventral Root ◽  
Common Mechanism ◽  
Renshaw Cells ◽  
Rat Diaphragm ◽  
Excitable Cells ◽  
End Plate ◽  
Root Stimulation

Studies on the rat diaphragm confirmed previous reports that histrionicotoxin (HTX) reversibly blocks contractions, miniature end-plate potentials and depolarizations by ACh. Microiontophoretic applications of HTX in anaesthetized cats reversibly blocked spontaneous and glutamate-evoked discharges of spinal and cortical neurones, and strongly depressed responses of Renshaw cells to ACh or ventral root stimulation. HTX blocked the excitation of cholinoceptive cortical neurones by ACh or glutamate, and concomitantly reduced spike amplitudes. The similarity between effects of HTX and procaine may indicate a common mechanism of action.

Dopamine exerts activation-dependent modulation of spinal locomotor circuits in the neonatal mouse

2012 ◽  
Vol 108 (12) ◽  
pp. 3370-3381 ◽  
Author(s):  
Jennifer M. Humphreys ◽  
Patrick J. Whelan
Keyword(s):  
Spinal Cord ◽  
Feedback Loops ◽  
Ventral Root ◽  
Neonatal Mouse ◽  
Network Activity ◽  
Mouse Spinal Cord ◽  
Network Function ◽  
Renshaw Cell ◽  
Root Stimulation ◽  
Excitatory Drive

Monoamines can modulate the output of a variety of invertebrate and vertebrate networks, including the spinal cord networks that control walking. Here we examined the multiple changes in the output of locomotor networks induced by dopamine (DA). We found that DA can depress the activation of locomotor networks in the neonatal mouse spinal cord following ventral root stimulation. By examining disinhibited rhythms, where the Renshaw cell pathway was blocked, we found that DA depresses a putative recurrent excitatory pathway that projects onto rhythm-generating circuitry of the spinal cord. This depression was D2 but not D1 receptor dependent and was not due exclusively to depression of excitatory drive to motoneurons. Furthermore, the depression in excitation was not dependent on network activity. We next compared the modulatory effects of DA on network function by focusing on a serotonin and a N-methyl-dl-aspartate-evoked rhythm. In contrast to the depressive effects on a ventral root-evoked rhythm, we found that DA stabilized a drug-evoked rhythm, reduced the frequency of bursting, and increased amplitude. Overall, these data demonstrate that DA can potentiate network activity while at the same time reducing the gain of recurrent excitatory feedback loops from motoneurons onto the network.

The Effects of Substance P and Baclofen on Motoneurones of Isolated Spinal Cord of the Newborn Rat

1980 ◽  
Vol 89 (1) ◽  
pp. 201-214
Author(s):  
MASANORI OTSUKA ◽  
MITSUHIKO YANAGISAWA
Keyword(s):  
Spinal Cord ◽  
Substance P ◽  
Ventral Root ◽  
Spinal Reflexes ◽  
Monosynaptic Reflex ◽  
Artificial Cerebrospinal Fluid ◽  
Site Of Action ◽  
Spinal Neurones ◽  
Depolarizing Agents ◽  
Root Stimulation

The effects of substance P (SP) and baclofen were studied in the isolated spinal cord of newborn rats. Potential changes generated in motoneurones were recorded extracellularly from the ventral root (L3-L5). When SP (8 × 10−5M) was introduced into the bath, the depolarization of motoneurones began with a delay of 1·1 s. A large part of this delay can be explained as a time needed for SP to reach the site of action on spinal neurones. When the preparation was perfused with artificial cerebrospinal fluid (CSF) containing low Ca (0·1 mM) and high Mg (1·6-3·5 mM), the spinal reflexes induced by dorsal root stimulation and recorded from the corresponding ventral root were completely abolished. The depolarizing action of SP (10−7M) on the motoneurones was potentiated in the low-Ca medium, suggesting that SP acts directly on the motoneurones. Baclofen at 10−6M depressed the monosynaptic reflex by about 75%. The SP-induced depolarization of motoneurones was greatly depressed by baclofen in both normal and 0·1 mM-Ca mediums. The effects of baclofen (10−6M) on the responses to various depolarizing agents were compared with that on the response to SP in artificial CSF containing 0·1 mM-Ca and 1·6-2 mM-Mg. The SP response was reduced by about 80%, whereas the responses to acetylcholine and glycine were not appreciably affected, and those to L-glutamate, GABA and noradrenaline were depressed by 10–22% by baclofen. These results suggest that baclofen blocks transmission at certain primary afferent synapses by antagonizing the action of SP that is released as a transmitter.

scholarly journals Effects of Baclofen on Spinal Reflexes and Persistent Inward Currents in Motoneurons of Chronic Spinal Rats With Spasticity

2004 ◽  
Vol 92 (5) ◽  
pp. 2694-2703 ◽  
Author(s):  
Y. Li ◽  
X. Li ◽  
P. J. Harvey ◽  
D. J. Bennett
Keyword(s):  
Spinal Cord ◽  
Ventral Root ◽  
Spinal Reflexes ◽  
Monosynaptic Reflex ◽  
Persistent Inward Currents ◽  
Inward Currents ◽  
Muscle Spasms ◽  
Acute Spinal Rats ◽  
Chronic Spinal Rats ◽  
Higher Doses

In the months after spinal cord injury, motoneurons develop large voltage-dependent persistent inward currents (PICs) that cause sustained reflexes and associated muscle spasms. These muscle spasms are triggered by any excitatory postsynaptic potential (EPSP) that is long enough to activate the PICs, which take >100 ms to activate. The PICs are composed of a persistent sodium current (Na PIC) and a persistent calcium current (Ca PIC). Considering that Ca PICs have been shown in other neurons to be inhibited by baclofen, we tested whether part of the antispastic action of baclofen was to reduce the motoneuron PICs as opposed to EPSPs. The whole sacrocaudal spinal cord from acute spinal rats and spastic chronic spinal rats (with sacral spinal transection 2 mo previously) was studied in vitro. Ventral root reflexes were recorded in response to dorsal root stimulation. Intracellular recordings were made from motoneurons, and slow voltage ramps were used to measure PICs. Chronic spinal rats exhibited large monosynaptic and long-lasting polysynaptic ventral root reflexes, and motoneurons had associated large EPSPs and PICs. Baclofen inhibited these reflexes at very low doses with a 50% inhibition (EC50) of the mono- and polysynaptic reflexes at 0.26 ± 0.07and 0.25 ± 0.09 (SD) μM, respectively. Baclofen inhibited the monosynaptic reflex in acute spinal rats at even lower doses (EC50 = 0.18 ± 0.02 μM). In chronic (and acute) spinal rats, all reflexes and EPSPs were eliminated with 1 μM baclofen with little change in motoneuron properties (PICs, input resistance, etc), suggesting that baclofen's antispastic action is presynaptic to the motoneuron. Unexpectedly, in chronic spinal rats higher doses of baclofen (20–30 μM) significantly increased the total motoneuron PIC by 31.6 ± 12.4%. However, the Ca PIC component (measured in TTX to block the Na PIC) was significantly reduced by baclofen. Thus baclofen increased the Na PIC and decreased the Ca PIC with a net increase in total PIC. By contrast, when a PIC was induced by 5-HT (10–30 μM) in motoneurons of acute spinal rats, baclofen (20–30 μM) significantly decreased the PIC by 38.8 ± 25.8%, primarily due to a reduction in the Ca PIC (measured in TTX), which dominated the total PIC in these acute spinal neurons. In summary, baclofen does not exert its antispastic action postsynaptically at clinically achievable doses (<1 μM), and at higher doses (10–30 μM), baclofen unexpectedly increases motoneuron excitability (Na PIC) in chronic spinal rats.

Neostriatal administration of somatostatin: differential effect of small and large doses on behavior and motor control

1977 ◽  
Vol 55 (2) ◽  
pp. 234-242 ◽  
Author(s):  
M. Rezek ◽  
V. Havlicek ◽  
L. Leybin ◽  
C. Pinsky ◽  
E. A. Kroeger ◽  
...  
Keyword(s):  
Motor Control ◽  
Eye Movements ◽  
Slow Wave ◽  
Rem Sleep ◽  
Differential Effect ◽  
Slow Wave Sleep ◽  
Small Doses ◽  
Freely Moving ◽  
Behavioral Excitation ◽  
Higher Doses

The administration of small doses of somatostatin (SRIF) (0.01 and 0.1 μg) into the neostriatal complex of unrestrained, freely moving rats induced general behavioral excitation associated with a variety of stereotyped movements, tremors, and a reduction of rapid eye movements (REM) and deep slow wave sleep (SWS). In contrast, the higher doses of SRIF (1.0 and 10.0 μg) caused movements to be uncoordinated and frequently induced more severe difficulties in motor control such as contralateral hemiplegia-in-extension which restricted or completely prevented the expression of normal behavioral patterns. As a result, the animals appeared drowsy and inhibited. Analysis of the sleep-waking cycle revealed prolonged periods of a shallow SWS while REM sleep and deep SWS were markedly reduced; electroencephalogram recordings revealed periods of dissociation from behavior. The administration of endocrinologically inactive as well as the active analogues of SRIF failed to induce effects comparable with those observed after the administration of the same dose of the native hormone (10.0 μg).

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.

Central sensitization following intradermal injection of capsaicin

1997 ◽  
Vol 20 (3) ◽  
pp. 471-471 ◽  
Author(s):  
William D. Willis
Keyword(s):  
Amino Acids ◽  
Substance P ◽  
Central Sensitization ◽  
Mechanical Allodynia ◽  
Excitatory Amino Acids ◽  
Intradermal Injection ◽  
Mechanical Hyperalgesia ◽  
Spinothalamic Tract ◽  
Nociceptive Neurons ◽  
Primary Hyperalgesia

Intradermal capsaicin in humans causes pain, primary hyperalgesia, and secondary mechanical hyperalgesia and allodynia. Parallel changes occur in the responses of primate spinothalamic tract cells and in rat behavior. Neurotransmitters that trigger secondary mechanical hyperalgesia and allodynia include excitatory amino acids and substance P. Secondary mechanical allodynia is actively maintained by central mechanisms. Our group has investigated mechanisms of central sensitization of nociceptive neurons by examining the responses to intradermal injection of capsaicin. These experiments are pertinent to issues raised by coderre & katz (sect. 2).

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