Some potassium channels express the transient outward current, I A, which recovers very rapidly from inactivation. One of these channels is Kv4.2. Kv4.2 is regulated by catecholamines such as epinephrine and dopamine. Evidence suggests that Kv4.2 is differentially expressed in functional subtypes of retinal ganglion cells (RGCs). Kv4.2-mediated currents regulate action potentials. Kv4.2 may regulate visual functions in the brain by altering the processing of inputs and by controlling the action potential outputs of RGCs. This dissertation addressed the contribution of potassium channels to RGC excitability. First, it was demonstrated how IA, and in particular IA generated by Kv4.2, modulates RGC excitability. Second, the hypothesis that dopamine modulates the function of action potentials via Kv4.2 channels in RGCs was tested. RGC morphology was determined in flat-mounted retinas by patch-filling ganglion cells with dye after recording the electrical properties. The properties of currents were determined via perforated-patch recordings. Action potentials were assayed in current-clamp configuration and currents were assayed in voltage-clamp configuration. IA was blocked by 4-AP and Kv4.2 IA currents were blocked by BaCl 2. Dopamine receptors were stimulated by a general dopamine agonist ADTN. 4-AP and BaCl2 affected the firing frequencies of RGCs while 4-AP additionally increased the duration of the transient maximum firing frequency and BaCl2 increased the transient maximum firing frequency itself. BaCl2 reduced the peak IA, but not the peak IK current. ADTN however affected properties of single action potentials, such as the voltage of the maximum firing frequency, the maximum dV/dt and the after-hyperpolarization amplitude. ADTN also reduced the peak IA and affected some biophysical properties of the IK. Indicating that IA potassium currents and Kv4.2 IA currents modulate overall firing rates in RGCs and dopamine modulates the shape of action potentials but not the overall firing rates of RGCs. This suggests that dopamine may act through potassium channels to regulate RGC excitability, but this interaction is not limited to just IA or IA mediated by Kv4.2 channels but works through potassium channels that contribute to the transient potassium current and single action potential properties.
|Advisor:||Myhr, Karen L.|
|Commitee:||Fischer, Thomas, Njus, David|
|School:||Wayne State University|
|School Location:||United States -- Michigan|
|Source:||MAI 48/04M, Masters Abstracts International|
|Keywords:||Dopamine, Excitability, Kv4.2, Potassium channels, Retina|
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