Distinct molecular targets including SLO-1 and gap junctions are engaged across a continuum of ethanol concentrations in Caenorhabditis elegans
Distinct molecular targets including SLO-1 and gap junctions are engaged across a continuum of ethanol concentrations in Caenorhabditis elegans
Ethanol (alcohol) interacts with diverse molecular effectors across a range of concentrations in the brain, eliciting intoxication through to sedation. Invertebrate models including the nematode worm Caenorhabditis elegans have been deployed for molecular genetic studies to inform on key components of these alcohol signaling pathways. C. elegans studies have typically employed external dosing with high (>250 mM) ethanol concentrations: A careful analysis of responses to low concentrations is lacking. Using the C. elegans pharyngeal system as a paradigm, we report a previously uncharacterized continuum of cellular and behavioral responses to ethanol from low (10 mM) to high (300 mM) concentrations. The complexity of these responses indicates that the pleiotropic action of ethanol observed in mammalian brain is conserved in this invertebrate model. We investigated two candidate ethanol effectors, the calcium-activated K(+) channel SLO-1 and gap junctions, and show that they contribute to, but are not sole determinants of, the low- and high-concentration effects, respectively. Notably, this study shows cellular and whole organismal behavioral responses to ethanol in C. elegans that directly equate to intoxicating through to supralethal blood alcohol concentrations in humans and provides an important benchmark for interpretation of paradigms that seek to inform on human alcohol use disorders.
alcohol, anesthesia, calcium-activated k+ channel, electrophysiology, intoxication, pharynx
4266-4278
Dillon, James
f406e30a-3ad4-4a53-80db-6694bab5e3ed
Andrianakis, Ioannis
130365dc-7914-4b33-87b2-92eca9da10a5
Mould, Richard
4f405a64-202d-4e3f-830c-65128e7f3da3
Ient, Ben
7768a9ec-82b6-4f5c-a921-b3041ffbb0ce
Liu, Wei
b64150aa-d935-4209-804d-24c1b97e024a
James, Christopher
c181ef38-6aec-4e52-8c57-48899e3534b5
O'Connor, Vincent
8021b06c-01a0-4925-9dde-a61c8fe278ca
Holden-Dye, Lindy
8032bf60-5db6-40cb-b71c-ddda9d212c8e
Dillon, James
f406e30a-3ad4-4a53-80db-6694bab5e3ed
Andrianakis, Ioannis
130365dc-7914-4b33-87b2-92eca9da10a5
Mould, Richard
4f405a64-202d-4e3f-830c-65128e7f3da3
Ient, Ben
7768a9ec-82b6-4f5c-a921-b3041ffbb0ce
Liu, Wei
b64150aa-d935-4209-804d-24c1b97e024a
James, Christopher
c181ef38-6aec-4e52-8c57-48899e3534b5
O'Connor, Vincent
8021b06c-01a0-4925-9dde-a61c8fe278ca
Holden-Dye, Lindy
8032bf60-5db6-40cb-b71c-ddda9d212c8e
Dillon, James, Andrianakis, Ioannis, Mould, Richard, Ient, Ben, Liu, Wei, James, Christopher, O'Connor, Vincent and Holden-Dye, Lindy
(2013)
Distinct molecular targets including SLO-1 and gap junctions are engaged across a continuum of ethanol concentrations in Caenorhabditis elegans.
The FASEB Journal, 27 (10), .
(doi:10.1096/fj.11-189340).
(PMID:23882127)
Abstract
Ethanol (alcohol) interacts with diverse molecular effectors across a range of concentrations in the brain, eliciting intoxication through to sedation. Invertebrate models including the nematode worm Caenorhabditis elegans have been deployed for molecular genetic studies to inform on key components of these alcohol signaling pathways. C. elegans studies have typically employed external dosing with high (>250 mM) ethanol concentrations: A careful analysis of responses to low concentrations is lacking. Using the C. elegans pharyngeal system as a paradigm, we report a previously uncharacterized continuum of cellular and behavioral responses to ethanol from low (10 mM) to high (300 mM) concentrations. The complexity of these responses indicates that the pleiotropic action of ethanol observed in mammalian brain is conserved in this invertebrate model. We investigated two candidate ethanol effectors, the calcium-activated K(+) channel SLO-1 and gap junctions, and show that they contribute to, but are not sole determinants of, the low- and high-concentration effects, respectively. Notably, this study shows cellular and whole organismal behavioral responses to ethanol in C. elegans that directly equate to intoxicating through to supralethal blood alcohol concentrations in humans and provides an important benchmark for interpretation of paradigms that seek to inform on human alcohol use disorders.
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e-pub ahead of print date: 23 July 2013
Keywords:
alcohol, anesthesia, calcium-activated k+ channel, electrophysiology, intoxication, pharynx
Organisations:
Biomedicine
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Local EPrints ID: 356785
URI: http://eprints.soton.ac.uk/id/eprint/356785
ISSN: 0892-6638
PURE UUID: 40f02b04-4ba2-4e7e-a5a0-b1c53b4b946f
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Date deposited: 23 Sep 2013 11:12
Last modified: 15 Mar 2024 03:17
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Author:
Ioannis Andrianakis
Author:
Richard Mould
Author:
Ben Ient
Author:
Christopher James
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