Block of voltage-gated potassium channels by Pacific ciguatoxin-1 contributes to increased neuronal excitability in rat sensory neurons

Birinyi-Strachan, LC; Gunning, SJ; Lewis, RJ; Nicholson, GM

Block of voltage-gated potassium channels by Pacific ciguatoxin-1 contributes to increased neuronal excitability in rat sensory neurons

Birinyi-Strachan, LC Gunning, SJ Lewis, RJ Nicholson, GM

Permalink

Publication Type:: Journal Article
Citation:: Toxicology and Applied Pharmacology, 2005, 204 (2), pp. 175 - 186
Issue Date:: 2005-04-15

Open Access

Copyright Clearance Process

Recently Added
In Progress
Open Access

This item is open access.

Adobe PDF

Download full textAdobe PDF (3.45 MB)

View on publisher's site

View statistics

Full metadata record

Field	Value	Language
dc.contributor.author	Birinyi-Strachan, LC	en_US
dc.contributor.author	Gunning, SJ	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	2004-08-31	en_US
dc.date.issued	2005-04-15	en_US
dc.identifier.citation	Toxicology and Applied Pharmacology, 2005, 204 (2), pp. 175 - 186	en_US
dc.identifier.issn	0041-008X	en_US
dc.identifier.uri	http://hdl.handle.net/10453/4825
dc.description.abstract	The present study investigated the actions of the polyether marine toxin Pacific ciguatoxin-1 (P-CTX-1) on neuronal excitability in rat dorsal root ganglion (DRG) neurons using patch-clamp recording techniques. Under current-clamp conditions, bath application of 2-20 nM P-CTX-1 caused a rapid, concentration-dependent depolarization of the resting membrane potential in neurons expressing tetrodotoxin (TTX)-sensitive voltage-gated sodium (Na v) channels. This action was completely suppressed by the addition of 200 nM TTX to the external solution, indicating that this effect was mediated through TTX-sensitive Nav channels. In addition, P-CTX-1 also prolonged action potential and afterhyperpolarization (AHP) duration. In a subpopulation of neurons, P-CTX-1 also produced tonic action potential firing, an effect that was not accompanied by significant oscillation of the resting membrane potential. Conversely, in neurons expressing TTX-resistant Na v currents, P-CTX-1 failed to alter any parameter of neuronal excitability examined in this study. Under voltage-clamp conditions in rat DRG neurons, P-CTX-1 inhibited both delayed-rectifier and 'A-type' potassium currents in a dose-dependent manner, actions that occurred in the absence of alterations to the voltage dependence of activation. These actions appear to underlie the prolongation of the action potential and AHP, and contribute to repetitive firing. These data indicate that a block of potassium channels contributes to the increase in neuronal excitability, associated with a modulation of Nav channel gating, observed clinically in response to ciguatera poisoning. © 2004 Elsevier Inc. All rights reserved.	en_US
dc.relation.ispartof	Toxicology and Applied Pharmacology	en_US
dc.relation.isbasedon	10.1016/j.taap.2004.08.020	en_US
dc.subject.classification	Toxicology	en_US
dc.subject.mesh	Ganglia, Spinal	en_US
dc.subject.mesh	Neurons, Afferent	en_US
dc.subject.mesh	Animals	en_US
dc.subject.mesh	Animals, Newborn	en_US
dc.subject.mesh	Eels	en_US
dc.subject.mesh	Rats	en_US
dc.subject.mesh	Rats, Wistar	en_US
dc.subject.mesh	Ciguatoxins	en_US
dc.subject.mesh	Tetrodotoxin	en_US
dc.subject.mesh	Potassium Channels, Voltage-Gated	en_US
dc.subject.mesh	Sodium Channels	en_US
dc.subject.mesh	Potassium Channel Blockers	en_US
dc.subject.mesh	Patch-Clamp Techniques	en_US
dc.subject.mesh	Electrophysiology	en_US
dc.subject.mesh	Membrane Potentials	en_US
dc.subject.mesh	Action Potentials	en_US
dc.subject.mesh	Dose-Response Relationship, Drug	en_US
dc.subject.mesh	Time Factors	en_US
dc.subject.mesh	Female	en_US
dc.subject.mesh	Male	en_US
dc.subject.mesh	NAV1.5 Voltage-Gated Sodium Channel	en_US
dc.title	Block of voltage-gated potassium channels by Pacific ciguatoxin-1 contributes to increased neuronal excitability in rat sensory neurons	en_US
dc.type	Journal Article
utslib.citation.volume	2	en_US
utslib.citation.volume	204	en_US
utslib.for	111506 Toxicology (incl. Clinical Toxicology)	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	2	en_US
pubs.publication-status	Published	en_US
pubs.volume	204	en_US

Abstract:

The present study investigated the actions of the polyether marine toxin Pacific ciguatoxin-1 (P-CTX-1) on neuronal excitability in rat dorsal root ganglion (DRG) neurons using patch-clamp recording techniques. Under current-clamp conditions, bath application of 2-20 nM P-CTX-1 caused a rapid, concentration-dependent depolarization of the resting membrane potential in neurons expressing tetrodotoxin (TTX)-sensitive voltage-gated sodium (Na v) channels. This action was completely suppressed by the addition of 200 nM TTX to the external solution, indicating that this effect was mediated through TTX-sensitive Nav channels. In addition, P-CTX-1 also prolonged action potential and afterhyperpolarization (AHP) duration. In a subpopulation of neurons, P-CTX-1 also produced tonic action potential firing, an effect that was not accompanied by significant oscillation of the resting membrane potential. Conversely, in neurons expressing TTX-resistant Na v currents, P-CTX-1 failed to alter any parameter of neuronal excitability examined in this study. Under voltage-clamp conditions in rat DRG neurons, P-CTX-1 inhibited both delayed-rectifier and 'A-type' potassium currents in a dose-dependent manner, actions that occurred in the absence of alterations to the voltage dependence of activation. These actions appear to underlie the prolongation of the action potential and AHP, and contribute to repetitive firing. These data indicate that a block of potassium channels contributes to the increase in neuronal excitability, associated with a modulation of Nav channel gating, observed clinically in response to ciguatera poisoning. © 2004 Elsevier Inc. All rights reserved.

Please use this identifier to cite or link to this item:

http://hdl.handle.net/10453/4825