The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Hans-georg Schaible - One of the best experts on this subject based on the ideXlab platform.
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ω Agatoxin IVA a p type calcium channel antagonist reduces nociceptive processing in spinal cord neurons with input from the inflamed but not from the normal knee joint an electrophysiological study in the rat in vivo
European Journal of Neuroscience, 1997Co-Authors: J. Nebe, Horacio Vanegas, Volker Neugebauer, Hans-georg SchaibleAbstract:High threshold voltage-dependent P- and Q-type calcium channels are involved in neurotransmitter release. In order to investigate the role of P- and Q-type calcium channels in the mechanosensory (nociceptive) processing in the spinal cord, their participation in the responses of spinal wide-dynamic-range neurons to innocuous and noxious mechanical stimulation of the knee and ankle joints was studied in 30 anaesthetized rats. The knee was either normal or acutely inflamed by kaolin/carrageenan. During the topical application of Omega-Agatoxin IVA (P-type channel antagonist, 0.1 microM) onto the dorsal surface of the spinal cord, the responses to innocuous and noxious pressure applied to the normal knee were increased to respectively 124 +/- 42% and 114 +/- 23% of predrug values (mean +/- SD, P < 0.05, 14 neurons). By contrast, in rats with an inflamed knee, the responses to innocuous and noxious pressure applied to the knee were reduced to respectively 72 +/- 19 and 73 +/- 22% of baseline (mean +/- SD, P < 0.01, 13 neurons). In the same neurons, Omega-Agatoxin IVA slightly increased the responses to pressure on the non-inflamed ankle whether the knee was normal or inflamed. Thus P-type calcium channels seem to acquire a predominant importance in the excitation of spinal cord neurons by mechanosensory input from inflamed tissue and hence in the generation of inflammatory pain. By contrast, the Q-type channel antagonist, Omega-conotoxin MVIIC (1 or 100 microM), had no significant effect upon responses to innocuous or noxious pressure applied to either normal or inflamed knees (25 neurons).
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Omega Agatoxin IVA a p type calcium channel antagonist reduces nociceptive processing in spinal cord neurons with input from the inflamed but not from the normal knee joint an electrophysiological study in the rat in vivo
European Journal of Neuroscience, 1997Co-Authors: J. Nebe, Horacio Vanegas, Volker Neugebauer, Hans-georg SchaibleAbstract:High threshold voltage-dependent P- and Q-type calcium channels are involved in neurotransmitter release. In order to investigate the role of P- and Q-type calcium channels in the mechanosensory (nociceptive) processing in the spinal cord, their participation in the responses of spinal wide-dynamic-range neurons to innocuous and noxious mechanical stimulation of the knee and ankle joints was studied in 30 anaesthetized rats. The knee was either normal or acutely inflamed by kaolin/carrageenan. During the topical application of Omega-Agatoxin IVA (P-type channel antagonist, 0.1 microM) onto the dorsal surface of the spinal cord, the responses to innocuous and noxious pressure applied to the normal knee were increased to respectively 124 +/- 42% and 114 +/- 23% of predrug values (mean +/- SD, P < 0.05, 14 neurons). By contrast, in rats with an inflamed knee, the responses to innocuous and noxious pressure applied to the knee were reduced to respectively 72 +/- 19 and 73 +/- 22% of baseline (mean +/- SD, P < 0.01, 13 neurons). In the same neurons, Omega-Agatoxin IVA slightly increased the responses to pressure on the non-inflamed ankle whether the knee was normal or inflamed. Thus P-type calcium channels seem to acquire a predominant importance in the excitation of spinal cord neurons by mechanosensory input from inflamed tissue and hence in the generation of inflammatory pain. By contrast, the Q-type channel antagonist, Omega-conotoxin MVIIC (1 or 100 microM), had no significant effect upon responses to innocuous or noxious pressure applied to either normal or inflamed knees (25 neurons).
Tom C. Cunnane - One of the best experts on this subject based on the ideXlab platform.
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Calcium channels controlling acetylcholine release in the guinea-pig isolated anterior pelvic ganglion: an electropharmacological study
Neuroscience, 1999Co-Authors: Amanda Smith, Tom C. CunnaneAbstract:An electropharmacological analysis of the type(s) of calcium channel controlling neurotransmitter release in preganglionic sympathetic nerve terminals in the guinea-pig anterior pelvic ganglion has been carried out. Conventional intracellular recording techniques were used to record excitatory postsynaptic potentials as a measure of neurotransmitter release. Excitatory postsynaptic potentials were abolished by hexamethonium (30-100 microM) and are therefore mediated by acetylcholine acting at nicotinic receptors. In studies of more than 150 cells, the N-type calcium channel blocker Omega-conotoxin GVIA (100-300 nM) failed to block the initiation of the nerve impulse by the excitatory postsynaptic potential. In single-cell studies, Omega-conotoxin GVIA (1 microM) sometimes altered the configuration of the excitatory postsynaptic potential/cell body nerve action potential complex, but on only one occasion was the excitatory postsynaptic potential reduced below the threshold required to initiate the action potential. Nifedipine (10 microM), Omega-Agatoxin IVA (100 nM) and Omega-conotoxin MVIIC (300 nM), applied alone or in combination with Omega-conotoxin GVIA (300 nM), were also ineffective. However, excitatory postsynaptic potentials evoked by trains of stimuli (0.1-0.5 Hz) were markedly reduced or abolished by the non-specific calcium channel blocker Omega-grammotoxin SIA (300 nM). When trains of stimuli were delivered at higher frequencies (4 Hz), the block induced by Omega-grammotoxin SIA could be overcome, and excitatory postsynaptic potentials were able to initiate action potentials even when Omega-conotoxin GVIA, Omega-Agatoxin IVA and Omega-conotoxin MVIIC were also present. The calcium channel(s) controlling acetylcholine release was (were) blocked by low concentrations of cadmium ions (30 microM) at all stimulation frequencies studied (0.1-50 Hz). Thus, the dominant calcium channels controlling acetylcholine release in sympathetic ganglia are not the L, N, P or Q types. At low frequencies of stimulation, Omega-grammotoxin SIA-sensitive calcium channels play a dominant role in acetylcholine release, but at higher stimulation frequencies yet another pharmacologically distinct calcium channel (or subtype) supports neurotransmitter release.
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Multiple calcium channels control neurotransmitter release from rat postganglionic sympathetic nerve terminals.
The Journal of Physiology, 1997Co-Authors: A B Smith, Tom C. CunnaneAbstract:1. Intracellular recording techniques were used to study neurotransmitter release mechanisms in postganglionic sympathetic nerve terminals of the rat isolated anococcygeus muscle. 2. Low concentrations of the N-type calcium channel blocker Omega-conotoxin GVIA (Omega-CgTX GVIA) irreversibly abolished excitatory junction potentials (EJPs) evoked by trains of < or = five stimuli at 10 Hz. When the frequency of stimulation was increased (10-50 Hz) trains of stimuli evoked EJPs even in the presence of 1 microM Omega-CgTX GVIA. We have termed this Omega-CgTX GVIA-resistant release 'residual release'. EJP amplitude in the presence of Omega-CgTX GVIA depended on both the frequency and number of stimuli in a train. 3. Residual release was inhibited by the P-type calcium channel blocker Omega-Agatoxin IVA (100 nM). However, even in the presence of both toxins, longer trains of stimuli could still evoke neurotransmitter release. 4. Residual release was abolished by Omega-conotoxin MVIIC and by the non-specific calcium channel antagonist Omega-grammotoxin SIA. Therefore, it would appear that a heterogeneous population of calcium channels is involved in mediating neurotransmitter release from these sympathetic nerve terminals.
C. C. Chang - One of the best experts on this subject based on the ideXlab platform.
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Calcium channel subtypes for the sympathetic and parasympathetic nerves of guinea-pig atria.
British Journal of Pharmacology, 1995Co-Authors: Shih-wun Hong, C. C. ChangAbstract:Abstract 1. The Ca2+ channel subtypes of the autonomic nerves of guinea-pig atria were elucidated by monitoring the effects of specific Ca2+ channel blockers on the negative and positive inotropic responses associated respectively, with stimulation of the parasympathetic and sympathetic nerves. 2. In left atria paced at 2-4 Hz, the negative inotropic effect induced by field stimulation of parasympathetic nerves (in the presence of propranolol) was abolished by Omega-conotoxin MVIIC, a blocker of N-type and OPQ subfamily Ca2+ channels. Omega-Conotoxin GVIA (an N-type blocker), Omega-Agatoxin IVA (a P-type blocker), nifedipine (an L-type blocker) and Ni2+ (a T- and R-type blocker) were much less effective. 3. The positive inotropic response resulting from field stimulation of the sympathetic nerves (in the presence of atropine) was abolished by both Omega-conotoxins, while Omega-Agatoxin IVA, nifedipine and Ni2+ were ineffective. 4. In the spontaneously beating right atria, the early negative inotropic effect produced by 1,1-dimethyl-4-phenylpiperazinium was abolished by Omega-conotoxin MVIIC, whereas the late positive inotropic effect was partially reduced, but not abolished, by a high concentration of Omega-conotoxin GVIA. 5. None of the peptide toxins affected the chronotropic and the inotropic responses evoked by carbachol and isoprenaline. 6. These results suggested that, under physiological conditions, the release of acetylcholine from parasympathetic nerves is dominated by an OPQ subfamily Ca2+ channel while that of noradrenaline from sympathetic nerves is controlled by an N-type Ca2+ channel. Ligand-induced noradrenaline release appeared to recruit additional type(s) of Ca2+ channel.
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Inhibition of acetylcholine release from mouse motor nerve by a P-type calcium channel blocker, Omega-Agatoxin IVA.
The Journal of Physiology, 1995Co-Authors: S.j. Hong, C. C. ChangAbstract:1. The effects were studied of the central neurone P-type Ca2+ channel blockers, Omega-Agatoxin IVA, Omega-conotoxin MVIIC (polypeptide toxins) and synthetic funnel-web spider polyamine toxin on acetylcholine release from mouse motor nerve. 2. Omega-Agatoxin IVA decreased the quantal content of endplate potentials and blocked synaptic transmission in the nanomolar range in a reversible manner, whereas the other toxins depressed transmission in the hundred micromolar range. 3. The polyamine toxin, but not the polypeptide toxins, decreased the amplitude of the miniature endplate potential. The increase in the frequency of miniature endplate potentials evoked by high [K+], but not that evoked by alpha-latrotoxin, was effectively antagonized by Omega-Agatoxin IVA. 4. In the presence of Omega-Agatoxin IVA, high frequency nerve stimulation produced facilitation of endplate currents and tetanic contractions. 5. The results suggest that, under physiological conditions, the Ca2+ necessary for nerve action potential-evoked acetylcholine release is translocated via a subtype of the P-type Ca2+ channel sensitive to Omega-Agatoxin IVA.
Amanda Smith - One of the best experts on this subject based on the ideXlab platform.
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Calcium channels controlling acetylcholine release in the guinea-pig isolated anterior pelvic ganglion: an electropharmacological study
Neuroscience, 1999Co-Authors: Amanda Smith, Tom C. CunnaneAbstract:An electropharmacological analysis of the type(s) of calcium channel controlling neurotransmitter release in preganglionic sympathetic nerve terminals in the guinea-pig anterior pelvic ganglion has been carried out. Conventional intracellular recording techniques were used to record excitatory postsynaptic potentials as a measure of neurotransmitter release. Excitatory postsynaptic potentials were abolished by hexamethonium (30-100 microM) and are therefore mediated by acetylcholine acting at nicotinic receptors. In studies of more than 150 cells, the N-type calcium channel blocker Omega-conotoxin GVIA (100-300 nM) failed to block the initiation of the nerve impulse by the excitatory postsynaptic potential. In single-cell studies, Omega-conotoxin GVIA (1 microM) sometimes altered the configuration of the excitatory postsynaptic potential/cell body nerve action potential complex, but on only one occasion was the excitatory postsynaptic potential reduced below the threshold required to initiate the action potential. Nifedipine (10 microM), Omega-Agatoxin IVA (100 nM) and Omega-conotoxin MVIIC (300 nM), applied alone or in combination with Omega-conotoxin GVIA (300 nM), were also ineffective. However, excitatory postsynaptic potentials evoked by trains of stimuli (0.1-0.5 Hz) were markedly reduced or abolished by the non-specific calcium channel blocker Omega-grammotoxin SIA (300 nM). When trains of stimuli were delivered at higher frequencies (4 Hz), the block induced by Omega-grammotoxin SIA could be overcome, and excitatory postsynaptic potentials were able to initiate action potentials even when Omega-conotoxin GVIA, Omega-Agatoxin IVA and Omega-conotoxin MVIIC were also present. The calcium channel(s) controlling acetylcholine release was (were) blocked by low concentrations of cadmium ions (30 microM) at all stimulation frequencies studied (0.1-50 Hz). Thus, the dominant calcium channels controlling acetylcholine release in sympathetic ganglia are not the L, N, P or Q types. At low frequencies of stimulation, Omega-grammotoxin SIA-sensitive calcium channels play a dominant role in acetylcholine release, but at higher stimulation frequencies yet another pharmacologically distinct calcium channel (or subtype) supports neurotransmitter release.
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Calcium channels controlling acetylcholine release from preganglionic nerve terminals in rat autonomic ganglia.
Neuroscience, 1999Co-Authors: Amanda Smith, Leonid Motin, Nickolas A. Lavidis, David J. AdamsAbstract:Little is known about the nature of the calcium channels controlling neurotransmitter release from preganglionic parasympathetic nerve fibres. In the present study, the effects of selective calcium channel antagonists and amiloride were investigated on ganglionic neurotransmission. Conventional intracellular recording and focal extracellular recording techniques were used in rat submandibular and pelvic ganglia, respectively. Excitatory postsynaptic potentials and excitatory postsynaptic currents preceded by nerve terminal impulses were recorded as a measure of acetylcholine release from parasympathetic and sympathetic preganglionic fibres following nerve stimulation. The calcium channel antagonists Omega-conotoxin GVIA (N type), nifedipine and nimodipine (L type), Omega-conotoxin MVIIC and Omega-Agatoxin IVA (P/Q type), and Ni2+ (R type) had no functional inhibitory effects on synaptic transmission in both submandibular and pelvic ganglia. The potassium-sparing diuretic, amiloride, and its analogue, dimethyl amiloride, produced a reversible and concentration-dependent inhibition of excitatory postsynaptic potential amplitude in the rat submandibular ganglion. The amplitude and frequency of spontaneous excitatory postsynaptic potentials and the sensitivity of the postsynaptic membrane to acetylcholine were unaffected by amiloride. In the rat pelvic ganglion, amiloride produced a concentration-dependent inhibition of excitatory postsynaptic currents without causing any detectable effects on the amplitude or configuration of the nerve terminal impulse. These results indicate that neurotransmitter release from preganglionic parasympathetic and sympathetic nerve terminals is resistant to inhibition by specific calcium channel antagonists of N-, L-, P/Q- and R-type calcium channels. Amiloride acts presynaptically to inhibit evoked transmitter release, but does not prevent action potential propagation in the nerve terminals, suggesting that amiloride may block the pharmacologically distinct calcium channel type(s) on rat preganglionic nerve terminals. (C) 1999 IBRO. Published by Elsevier Science Ltd.
J. Nebe - One of the best experts on this subject based on the ideXlab platform.
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ω Agatoxin IVA a p type calcium channel antagonist reduces nociceptive processing in spinal cord neurons with input from the inflamed but not from the normal knee joint an electrophysiological study in the rat in vivo
European Journal of Neuroscience, 1997Co-Authors: J. Nebe, Horacio Vanegas, Volker Neugebauer, Hans-georg SchaibleAbstract:High threshold voltage-dependent P- and Q-type calcium channels are involved in neurotransmitter release. In order to investigate the role of P- and Q-type calcium channels in the mechanosensory (nociceptive) processing in the spinal cord, their participation in the responses of spinal wide-dynamic-range neurons to innocuous and noxious mechanical stimulation of the knee and ankle joints was studied in 30 anaesthetized rats. The knee was either normal or acutely inflamed by kaolin/carrageenan. During the topical application of Omega-Agatoxin IVA (P-type channel antagonist, 0.1 microM) onto the dorsal surface of the spinal cord, the responses to innocuous and noxious pressure applied to the normal knee were increased to respectively 124 +/- 42% and 114 +/- 23% of predrug values (mean +/- SD, P < 0.05, 14 neurons). By contrast, in rats with an inflamed knee, the responses to innocuous and noxious pressure applied to the knee were reduced to respectively 72 +/- 19 and 73 +/- 22% of baseline (mean +/- SD, P < 0.01, 13 neurons). In the same neurons, Omega-Agatoxin IVA slightly increased the responses to pressure on the non-inflamed ankle whether the knee was normal or inflamed. Thus P-type calcium channels seem to acquire a predominant importance in the excitation of spinal cord neurons by mechanosensory input from inflamed tissue and hence in the generation of inflammatory pain. By contrast, the Q-type channel antagonist, Omega-conotoxin MVIIC (1 or 100 microM), had no significant effect upon responses to innocuous or noxious pressure applied to either normal or inflamed knees (25 neurons).
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Omega Agatoxin IVA a p type calcium channel antagonist reduces nociceptive processing in spinal cord neurons with input from the inflamed but not from the normal knee joint an electrophysiological study in the rat in vivo
European Journal of Neuroscience, 1997Co-Authors: J. Nebe, Horacio Vanegas, Volker Neugebauer, Hans-georg SchaibleAbstract:High threshold voltage-dependent P- and Q-type calcium channels are involved in neurotransmitter release. In order to investigate the role of P- and Q-type calcium channels in the mechanosensory (nociceptive) processing in the spinal cord, their participation in the responses of spinal wide-dynamic-range neurons to innocuous and noxious mechanical stimulation of the knee and ankle joints was studied in 30 anaesthetized rats. The knee was either normal or acutely inflamed by kaolin/carrageenan. During the topical application of Omega-Agatoxin IVA (P-type channel antagonist, 0.1 microM) onto the dorsal surface of the spinal cord, the responses to innocuous and noxious pressure applied to the normal knee were increased to respectively 124 +/- 42% and 114 +/- 23% of predrug values (mean +/- SD, P < 0.05, 14 neurons). By contrast, in rats with an inflamed knee, the responses to innocuous and noxious pressure applied to the knee were reduced to respectively 72 +/- 19 and 73 +/- 22% of baseline (mean +/- SD, P < 0.01, 13 neurons). In the same neurons, Omega-Agatoxin IVA slightly increased the responses to pressure on the non-inflamed ankle whether the knee was normal or inflamed. Thus P-type calcium channels seem to acquire a predominant importance in the excitation of spinal cord neurons by mechanosensory input from inflamed tissue and hence in the generation of inflammatory pain. By contrast, the Q-type channel antagonist, Omega-conotoxin MVIIC (1 or 100 microM), had no significant effect upon responses to innocuous or noxious pressure applied to either normal or inflamed knees (25 neurons).
