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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.
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.
Creator
Kuchera, Claire Rice, Stackman, Robert W., Graduate College
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...
Show moreSmall 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.
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Date Issued
2014
PURL
http://purl.flvc.org/fau/fd/FA00005830
Format
Document (PDF)
In vivo administration of a subtype selective activator of small conductance Ca2+ - activated K+ channels influences hippocampal-dependent spatial memory
Title
In vivo administration of a subtype selective activator of small conductance Ca2+ - activated K+ channels influences hippocampal-dependent spatial memory.
Creator
Beck, Robert, Kuchera, Claire Rice, Munchow, Alcira H., Stackman, Robert W., Graduate College
Date Issued
2013-04-12
PURL
http://purl.flvc.org/fcla/dt/3361271
Subject Headings
Calcium-dependent potassium channels, Hippocampus (Brain), Mice, Memory
Format
Document (PDF)
Selective Activation of the SK1 Subtype of Small Conductance Ca2+ Activated K+ Channels by GW542573X in C57BL6J Mice Impairs Hippocampal-dependent Memory
Title
Selective Activation of the SK1 Subtype of Small Conductance Ca2+ Activated K+ Channels by GW542573X in C57BL6J Mice Impairs Hippocampal-dependent Memory.
Creator
Rice Kuchera, Claire A., Stackman, Robert W., Florida Atlantic University, Charles E. Schmidt College of Science, Department of Psychology
Abstract/Description
SK channels are small conductance Ca2+-activated K+ channels expressed throughout the CNS. SK channels modulate the excitability of hippocampal CA1 neurons by affecting afterhyperpolarization and shaping excitatory postsynaptic responses. Such SK-mediated effects on activity-dependent neuronal excitability and synaptic strength are thought to underlie the modulatory influence of SK channels on memory encoding. Here,the effect of a new SK1 selective activator, GW542573X, on hippocampal...
Show moreSK channels are small conductance Ca2+-activated K+ channels expressed throughout the CNS. SK channels modulate the excitability of hippocampal CA1 neurons by affecting afterhyperpolarization and shaping excitatory postsynaptic responses. Such SK-mediated effects on activity-dependent neuronal excitability and synaptic strength are thought to underlie the modulatory influence of SK channels on memory encoding. Here,the effect of a new SK1 selective activator, GW542573X, on hippocampal-dependent object memory, contextual and cued conditioning, and trace fear conditioning was examined. The results demonstrated that pre- but not post-training systemic administration of GW542573X impaired object memory and trace fear memory in mice 24 h after training. Contextual and cued fear memory were not disrupted. These current data suggest that activation of SK1 subtype-containing SK channels impairs long-term memory. These results are consistent with converging evidence that SK channel activation suppressed behaviorally triggered synaptic plasticity necessary for encoding hippocampal-dependent memory.
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Date Issued
2015
PURL
http://purl.flvc.org/fau/fd/FA00004541, http://purl.flvc.org/fau/fd/FA00004541
Subject Headings
Cellular control mechanisms, Cognitive neuroscience, Cognitive psychology, Hippocampus (Brain), Mice as laboratory animals, Neurotransmitter receptors
Format
Document (PDF)