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Selective Activation of the SK1 Subtype of Small Conductance Ca2+-Activated K+Channels by 4-(2-Methoxyphenylcarbamoyloxymethyl)-piperidine-l-carboxylic Acid tert-Butyl Ester(GW542573X) in C57BL/6J Mice lmpairs Hippocampal-Dependent Memory.

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Date Issued:
2014
Abstract/Description:
Small conductance Ca2+ -activated K+ (SK) channels have physiological roles in learning and memory, intrinsic excitability, synaptic transmission and plasticity, and addiction. While SK2 and SK3 channels have been studied, the role of SK1 has not yet been determined due to the prior lack of gene-specific antibodies and agonists. SK1 are robustly expressed in the CA1 pyramidal neurons of the hippocampus and modulate their excitability by affecting afterhyperpolarization. SK1 subunits are only sited in the plasma membrane when co-expressed with SK2 or SK3. Co-expressed and co-assembled SK1, SK2, and SK3 subunits form functional apamin-sensitive channels. SK1 are not apamin selective, suggesting the overriding hypothesis that SK1 is a subunit of heteromeric SK channels that bind specific interacting proteins. We examined the effect of a new SK1 selective activator, GW542573X, on hippocampal dependent object memory in male C57BL/6J mice. The results showed that activating SK1 channels by systemic injection of the SK1 agonist GW542573X before the sample session, led to impaired object memory in mice 24 h later. Mice treated with GW542573X acquired the sample object exploration criterion in a similar latency as the vehicle-treated mice.GW542573X treated mice exhibited significantly less preference for exploring the novel object during the test session compared to the vehicle-treated mice. These results suggest that the SK1 activator disrupted the encoding of object memory without affecting the motivation to explore objects. This supports a role for SK1 in the modulation of hippocampal synaptic plasticity and hippocampal-dependent memory.
Title: Selective Activation of the SK1 Subtype of Small Conductance Ca2+-Activated K+Channels by 4-(2-Methoxyphenylcarbamoyloxymethyl)-piperidine-l-carboxylic Acid tert-Butyl Ester(GW542573X) in C57BL/6J Mice lmpairs Hippocampal-Dependent Memory.
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Name(s): Kuchera, Claire Rice
Stackman, Robert W.
Graduate College
Type of Resource: text
Genre: Abstract
Date Created: 2014
Date Issued: 2014
Publisher: Florida Atlantic University
Place of Publication: Boca Raton, Fla.
Physical Form: application/pdf
Extent: 1 p.
Language(s): English
Abstract/Description: Small conductance Ca2+ -activated K+ (SK) channels have physiological roles in learning and memory, intrinsic excitability, synaptic transmission and plasticity, and addiction. While SK2 and SK3 channels have been studied, the role of SK1 has not yet been determined due to the prior lack of gene-specific antibodies and agonists. SK1 are robustly expressed in the CA1 pyramidal neurons of the hippocampus and modulate their excitability by affecting afterhyperpolarization. SK1 subunits are only sited in the plasma membrane when co-expressed with SK2 or SK3. Co-expressed and co-assembled SK1, SK2, and SK3 subunits form functional apamin-sensitive channels. SK1 are not apamin selective, suggesting the overriding hypothesis that SK1 is a subunit of heteromeric SK channels that bind specific interacting proteins. We examined the effect of a new SK1 selective activator, GW542573X, on hippocampal dependent object memory in male C57BL/6J mice. The results showed that activating SK1 channels by systemic injection of the SK1 agonist GW542573X before the sample session, led to impaired object memory in mice 24 h later. Mice treated with GW542573X acquired the sample object exploration criterion in a similar latency as the vehicle-treated mice.GW542573X treated mice exhibited significantly less preference for exploring the novel object during the test session compared to the vehicle-treated mice. These results suggest that the SK1 activator disrupted the encoding of object memory without affecting the motivation to explore objects. This supports a role for SK1 in the modulation of hippocampal synaptic plasticity and hippocampal-dependent memory.
Identifier: FA00005830 (IID)
Collection: FAU Student Research Digital Collection
Note(s): The Fifth Annual Graduate Research Day was organized by Florida Atlantic University’s Graduate Student Association. Graduate students from FAU Colleges present abstracts of original research and posters in a competition for monetary prizes, awards, and recognition
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Sublocation: Digital Library
Persistent Link to This Record: http://purl.flvc.org/fau/fd/FA00005830
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Host Institution: FAU
Is Part of Series: Florida Atlantic University Digital Library Collections.