Neuroprotectant effects of iso-osmolar D-mannitol to prevent Pacific ciguatoxin-1 induced alterations in neuronal excitability: A comparison with other osmotic agents and free radical scavengers

Birinyi-Strachan, LC; Davies, MJ; Lewis, RJ; Nicholson, GM

Neuroprotectant effects of iso-osmolar D-mannitol to prevent Pacific ciguatoxin-1 induced alterations in neuronal excitability: A comparison with other osmotic agents and free radical scavengers

Birinyi-Strachan, LC Davies, MJ Lewis, RJ Nicholson, GM

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Publication Type:: Journal Article
Citation:: Neuropharmacology, 2005, 49 (5), pp. 669 - 686
Issue Date:: 2005-10-01

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Field	Value	Language
dc.contributor.author	Birinyi-Strachan, LC	en_US
dc.contributor.author	Davies, MJ	en_US
dc.contributor.author	Lewis, RJ	en_US
dc.contributor.author	Nicholson, GM https://orcid.org/0000-0002-4277-4296	en_US
dc.date.available	2005-04-25	en_US
dc.date.issued	2005-10-01	en_US
dc.identifier.citation	Neuropharmacology, 2005, 49 (5), pp. 669 - 686	en_US
dc.identifier.issn	0028-3908	en_US
dc.identifier.uri	http://hdl.handle.net/10453/4641
dc.description.abstract	The basis for the neuroprotectant effect of D-mannitol in reducing the sensory neurological disturbances seen in ciguatera poisoning, is unclear. Pacific ciguatoxin-1 (P-CTX-1), at a concentration 10 nM, caused a statistically significant swelling of rat sensory dorsal root ganglia (DRG) neurons that was reversed by hyperosmolar 50 mM D-mannitol. However, using electron paramagnetic resonance (EPR) spectroscopy, it was found that P-CTX-1 failed to generate hydroxyl free radicals at concentrations of toxin that caused profound effects on neuronal excitability. Whole-cell patch-clamp recordings from DRG neurons revealed that both hyper- and iso-osmolar 50 mM D-mannitol prevented the membrane depolarisation and repetitive firing of action potentials induced by P-CTX-1. In addition, both hyper- and iso-osmolar 50 mM D-mannitol prevented the hyperpolarising shift in steady-state inactivation and the rise in leakage current through tetrodotoxin (TTX)-sensitive Nav channels, as well as the increased rate of recovery from inactivation of TTX-resistant Na v channels induced by P-CTX-1. D-Mannitol also reduced, but did not prevent, the inhibition of peak TTX-sensitive and TTX-resistant INa amplitude by P-CTX-1. Additional experiments using hyper- and iso-osmolar d-sorbitol, hyperosmolar sucrose and the free radical scavenging agents Trolox® and L-ascorbic acid showed that these agents, unlike D-mannitol, failed to prevent the effects of P-CTX-1 on spike electrogenesis and Na v channel gating. These selective actions of D-mannitol indicate that it does not act purely as an osmotic agent to reduce swelling of nerves, but involves a more complex action dependent on the Nav channel subtype, possibly to alter or reduce toxin association. © 2005 Elsevier Ltd. All rights reserved.	en_US
dc.relation.ispartof	Neuropharmacology	en_US
dc.relation.isbasedon	10.1016/j.neuropharm.2005.04.024	en_US
dc.subject.classification	Neurology & Neurosurgery	en_US
dc.subject.mesh	Ganglia, Spinal	en_US
dc.subject.mesh	Neurons, Afferent	en_US
dc.subject.mesh	Mannitol	en_US
dc.subject.mesh	Sorbitol	en_US
dc.subject.mesh	Ascorbic Acid	en_US
dc.subject.mesh	Ciguatoxins	en_US
dc.subject.mesh	Chromans	en_US
dc.subject.mesh	Tetrodotoxin	en_US
dc.subject.mesh	Sodium Channels	en_US
dc.subject.mesh	Neuroprotective Agents	en_US
dc.subject.mesh	Sodium Channel Blockers	en_US
dc.subject.mesh	Diuretics	en_US
dc.subject.mesh	Free Radical Scavengers	en_US
dc.subject.mesh	Electron Spin Resonance Spectroscopy	en_US
dc.subject.mesh	Patch-Clamp Techniques	en_US
dc.subject.mesh	Electrophysiology	en_US
dc.subject.mesh	Cell Size	en_US
dc.subject.mesh	Ion Channel Gating	en_US
dc.subject.mesh	Membrane Potentials	en_US
dc.subject.mesh	Osmolar Concentration	en_US
dc.subject.mesh	Algorithms	en_US
dc.title	Neuroprotectant effects of iso-osmolar D-mannitol to prevent Pacific ciguatoxin-1 induced alterations in neuronal excitability: A comparison with other osmotic agents and free radical scavengers	en_US
dc.type	Journal Article
utslib.citation.volume	5	en_US
utslib.citation.volume	49	en_US
utslib.for	1701 Psychology	en_US
utslib.for	1109 Neurosciences	en_US
utslib.for	1115 Pharmacology and Pharmaceutical Sciences	en_US
dc.location.activity	UNIV SYDNEY, SYDNEY, AUSTRALIA
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Strength - CHT - Health Technologies
utslib.copyright.status	open_access
pubs.issue	5	en_US
pubs.publication-status	Published	en_US
pubs.volume	49	en_US

Abstract:

The basis for the neuroprotectant effect of D-mannitol in reducing the sensory neurological disturbances seen in ciguatera poisoning, is unclear. Pacific ciguatoxin-1 (P-CTX-1), at a concentration 10 nM, caused a statistically significant swelling of rat sensory dorsal root ganglia (DRG) neurons that was reversed by hyperosmolar 50 mM D-mannitol. However, using electron paramagnetic resonance (EPR) spectroscopy, it was found that P-CTX-1 failed to generate hydroxyl free radicals at concentrations of toxin that caused profound effects on neuronal excitability. Whole-cell patch-clamp recordings from DRG neurons revealed that both hyper- and iso-osmolar 50 mM D-mannitol prevented the membrane depolarisation and repetitive firing of action potentials induced by P-CTX-1. In addition, both hyper- and iso-osmolar 50 mM D-mannitol prevented the hyperpolarising shift in steady-state inactivation and the rise in leakage current through tetrodotoxin (TTX)-sensitive Nav channels, as well as the increased rate of recovery from inactivation of TTX-resistant Na v channels induced by P-CTX-1. D-Mannitol also reduced, but did not prevent, the inhibition of peak TTX-sensitive and TTX-resistant INa amplitude by P-CTX-1. Additional experiments using hyper- and iso-osmolar d-sorbitol, hyperosmolar sucrose and the free radical scavenging agents Trolox® and L-ascorbic acid showed that these agents, unlike D-mannitol, failed to prevent the effects of P-CTX-1 on spike electrogenesis and Na v channel gating. These selective actions of D-mannitol indicate that it does not act purely as an osmotic agent to reduce swelling of nerves, but involves a more complex action dependent on the Nav channel subtype, possibly to alter or reduce toxin association. © 2005 Elsevier Ltd. All rights reserved.

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http://hdl.handle.net/10453/4641