CONTRIBUTIONS OF EAG PROTEIN TO NEURONAL EXCITABILITY IN IDENTIFIED THORACIC MOTONEURONS OF DROSOPHILA

Persistent Link:
http://hdl.handle.net/10150/194828
Title:
CONTRIBUTIONS OF EAG PROTEIN TO NEURONAL EXCITABILITY IN IDENTIFIED THORACIC MOTONEURONS OF DROSOPHILA
Author:
Srinivasan, Subhashini
Issue Date:
2010
Publisher:
The University of Arizona.
Rights:
Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
Abstract:
Diversity in the expression of ion channel proteins among neurons allows a wide range of excitability, growth and functional regulation. Ether-a-go-go (EAG), a member of the voltage-gated K+ channels, was characterized by spontaneous firing in nerve terminals and enhanced neurotransmitter release. In situ whole-cell patch-clamp recordings performed from the somata of Drosophila larval thoracic aCC motoneurons revealed spontaneous spike-like events in eag mutants. Spontaneous events were absent in wild type motoneurons. Spikes evoked by somatic current injection in to the cell body were not altered and comparable to wild type. Spontaneous spike-like events could be due to increased synaptic drive or altered intrinsic excitability of the motoneuron. Reduction of EAG function with selective expression of eag double stranded RNAi transgene in motoneurons only did not cause spontaneous spike-like events or alter evoked firing. This suggests increased synaptic drive contributes to spontaneous events.Both transient and sustained voltage-activated K+ currents, each with Ca++-sensitive (IA(Ca) and IK(Ca)) and Ca++ -insensitive components (IA and IK), were isolated in thoracic aCC motoneurons. In wild type motoneurons, IA was larger than IA(Ca). Conversely, IK(Ca) was larger than IK. Both eag mutants and eag RNAi expression resulted in a decrease in IA , IK and a slow sustained K+ current. Further, EAG and Shal demonstrate a potential functional interaction and contribute to IA. The voltage sensitivity for inactivation was reduced in Shal only and EAG-Shal double knock down compared to controls and EAG only knock down. In addition, a Ca++ sensitive EAG dependent K+ current was blocked by cAMP. Thus, both voltage-dependent and modulatory functions of EAG influence excitability in motoneurons.Firing properties and K+ currents distinguish aCC motoneurons in thoracic segments, T1 and T3. T3aCC had a shorter delay to spike, higher input resistance and were more easily recruited than T1aCC. T1aCC had a larger IA than T3aCC, but comparable IA(Ca). IK(Ca) was larger in T3aCC compared to T1aCC. These differences reflect cell-specific ion channel distribution that could contribute to patterned segmental motor output.
Type:
text; Electronic Dissertation
Keywords:
Drosophila; Excitability; Motoneuron; Patch-clamp; Potassium channel
Degree Name:
Ph.D.
Degree Level:
doctoral
Degree Program:
Physiological Sciences; Graduate College
Degree Grantor:
University of Arizona
Advisor:
Levine, Richard B.
Committee Chair:
Levine, Richard B.

Full metadata record

DC FieldValue Language
dc.language.isoenen_US
dc.titleCONTRIBUTIONS OF EAG PROTEIN TO NEURONAL EXCITABILITY IN IDENTIFIED THORACIC MOTONEURONS OF DROSOPHILAen_US
dc.creatorSrinivasan, Subhashinien_US
dc.contributor.authorSrinivasan, Subhashinien_US
dc.date.issued2010en_US
dc.publisherThe University of Arizona.en_US
dc.rightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.en_US
dc.description.abstractDiversity in the expression of ion channel proteins among neurons allows a wide range of excitability, growth and functional regulation. Ether-a-go-go (EAG), a member of the voltage-gated K+ channels, was characterized by spontaneous firing in nerve terminals and enhanced neurotransmitter release. In situ whole-cell patch-clamp recordings performed from the somata of Drosophila larval thoracic aCC motoneurons revealed spontaneous spike-like events in eag mutants. Spontaneous events were absent in wild type motoneurons. Spikes evoked by somatic current injection in to the cell body were not altered and comparable to wild type. Spontaneous spike-like events could be due to increased synaptic drive or altered intrinsic excitability of the motoneuron. Reduction of EAG function with selective expression of eag double stranded RNAi transgene in motoneurons only did not cause spontaneous spike-like events or alter evoked firing. This suggests increased synaptic drive contributes to spontaneous events.Both transient and sustained voltage-activated K+ currents, each with Ca++-sensitive (IA(Ca) and IK(Ca)) and Ca++ -insensitive components (IA and IK), were isolated in thoracic aCC motoneurons. In wild type motoneurons, IA was larger than IA(Ca). Conversely, IK(Ca) was larger than IK. Both eag mutants and eag RNAi expression resulted in a decrease in IA , IK and a slow sustained K+ current. Further, EAG and Shal demonstrate a potential functional interaction and contribute to IA. The voltage sensitivity for inactivation was reduced in Shal only and EAG-Shal double knock down compared to controls and EAG only knock down. In addition, a Ca++ sensitive EAG dependent K+ current was blocked by cAMP. Thus, both voltage-dependent and modulatory functions of EAG influence excitability in motoneurons.Firing properties and K+ currents distinguish aCC motoneurons in thoracic segments, T1 and T3. T3aCC had a shorter delay to spike, higher input resistance and were more easily recruited than T1aCC. T1aCC had a larger IA than T3aCC, but comparable IA(Ca). IK(Ca) was larger in T3aCC compared to T1aCC. These differences reflect cell-specific ion channel distribution that could contribute to patterned segmental motor output.en_US
dc.typetexten_US
dc.typeElectronic Dissertationen_US
dc.subjectDrosophilaen_US
dc.subjectExcitabilityen_US
dc.subjectMotoneuronen_US
dc.subjectPatch-clampen_US
dc.subjectPotassium channelen_US
thesis.degree.namePh.D.en_US
thesis.degree.leveldoctoralen_US
thesis.degree.disciplinePhysiological Sciencesen_US
thesis.degree.disciplineGraduate Collegeen_US
thesis.degree.grantorUniversity of Arizonaen_US
dc.contributor.advisorLevine, Richard B.en_US
dc.contributor.chairLevine, Richard B.en_US
dc.contributor.committeememberDuch, Carstenen_US
dc.contributor.committeememberFuglevand, Andrewen_US
dc.contributor.committeememberFregosi, Ralphen_US
dc.identifier.proquest11166en_US
dc.identifier.oclc752261020en_US
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