The role of subthreshold voltage-gated potassium channel currents in the development of neurological disorders
Open Access
- Author:
- Sberna, Anna Paulett
- Graduate Program:
- Genetics
- Degree:
- Master of Science
- Document Type:
- Master Thesis
- Date of Defense:
- April 04, 2014
- Committee Members:
- Timothy J Jegla, Thesis Advisor/Co-Advisor
- Keywords:
- subthreshold
A-current
M-current
Kv4
Kv7
epilepsy
schizophrenia - Abstract:
- Voltage-gated potassium channels are critical in maintaining proper neuron signaling and excitability in the mammalian CNS. While there are a variety of diverse types of K+ currents, this thesis focuses specifically on subthreshold currents in the mammalian hippocampus and how they can affect the development of neurological disorders. The hippocampal region is particularly important not only in learning and memory formation but as a hot spot for the study of neurological diseases such as epilepsies and schizophrenia. Studies regarding the roles of the subthreshold voltage-gated K+ currents, including the A-type and M-type currents, have elucidated new relationships between channel mutations and epilepsies. Disruptions in the M-current have already been identified in the pathogenesis of benign familial neonatal seizures while the A-current is potentially involved in the development of temporal lobe epilepsy. Further connections can be made that implicate the M-current in other neurological disorders, particularly schizophrenia. The Kv7 channels that produce the widely studied, specialized M-current have already led to the discovery of the drug retigabine. This selective channel opener has been useful in past research regarding the role of the M-current in idiopathic epilepsies. However, retigabine and several Kv7 channel blockers may also be important in future studies that endeavor to understand how the M-current is involved in schizophrenia. Using the currently available literature, this thesis seeks to expand upon our current knowledge of the subthreshold A- and M-currents as they pertain to the pathophysiologies of neurological disorders.