TitleIon channel profiles in murine spiral ganglion neurons
NameChen, Wei Chun (author), Hsu, Shu-Chan (chair), Davis, Robin L. (internal member), Plummer, Mark R. (internal member), Dreyfus, Cheryl F, (internal member), Olson, Elizabeth S. (outside member), Rutgers University, Graduate School - New Brunswick,
DescriptionSpiral ganglion neurons possess a rich repertoire of ion channels that underlies differential firing properties. Previous studies have shown that voltage-gated K+ channels (Kv1.1, Kv3.1, Kv4.2, and BK) are arranged in a tonotopic manner along the length of cochlea. The present study will expand the analysis to three additional classes of ion channels: two-pore-domain K+ channels (K2Ps), voltage-gated Ca2+ channels (VGCCs), and Ca2+-activated K+ channels; in order to determine their contribution to the tonotopic organization in these primary afferent neurons. Transcript profiling was first used to survey candidate subunits. A subset of K2P subunit transcripts (TASK-1, TASK-3, THIK-2, TRAAK, TREK-1, and TWIK-1) were identified in the spiral ganglion; of which TWIK-1 was the most abundantly expressed and was confirmed to localize to neurons. Of the ten VGCC subunits, eight transcripts (Cav1.2, Cav1.3, Cav2.1, Cav2.2, Cav2.3, Cav3.1, Cav3.2, and Cav3.3) were expressed. Immunocytochemistry showed that three subunits (Cav1.3, Cav2.2, and Cav3.3) were specifically localized to neurons and tonotopically distributed, which provided insights to the electrophysiological results that demonstrated the involvement of both HVA and LVA VGCCs in differential regulation of action potential duration and latency, respectively. Lastly, of the Ca2+-activated K+ channel subunits, BKalpha, BKbeta1, BKbeta2, BKbeta4, SK1, SK2, and SK3 transcripts were identified. Examination of the two BKalpha splice sites showed only a single prominent ZERO variant, which suggested that BK beta-subunit regulation may possibly be the main mechanisms of BK channel contribution to the firing properties. Antibody labeling of BKbeta4 subunit showed uniform distribution. Future work will further investigate the remaining beta-subunits. Taken together, K2Ps, VGCCs, and Ca2+-activated K+ channels could all potentially, although not necessary directly, influence neuronal excitability and action potential waveforms, thus demonstrating the complexity in underlying diversity of spiral ganglion neuron firing patterns.
NoteIncludes bibliographical references
Noteby Wei Chun Chen
CollectionGraduate School - New Brunswick Electronic Theses and Dissertations
Organization NameRutgers, The State University of New Jersey
RightsThe author owns the copyright to this work.