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J. A. deVries, M. Beri, K. L. Myhr; Kv4.2-Mediated Potassium Currents Contribute to Action Potential Generation in Retinal Ganglion Cells. Invest. Ophthalmol. Vis. Sci. 2010;51(13):1858.
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Kv4.2 is a fast activating, fast inactivating voltage-gated potassium channel that can be regulated by catecholamines, such as epinephrine and dopamine. It contributes to the transient IA current. Evidence suggests that Kv4.2 is differentially expressed in functional subtypes of retinal ganglion cells (RGCs), including those associated with the circadian cycle and form vision. We propose that Kv4.2 modulates the action potentials of these RGCs and may be regulated by dopamine.
Mouse retinae were acutely isolated and flat mounted on filter paper. Somas of single RGCs were current-clamped to assay action potentials and firing patterns and voltage-clamped to assay potassium current profiles. Potassium channel blockers were used to determine the role of currents on RGC action potential output; and dopamine agonists were used to determine the effects of dopamine on potassium currents and action potentials in RGCs. RGCs were filled with dye and immunohistochemistry was used post hoc to determine whether recorded cells expressed Kv4.2.
Subpopulations of RGCs with prominent IA showed a reduction in IA current by bath application of 400 µM BaCl2, which has been shown to block Kv4.2 currents in other types of neurons. Consistent with this, RGCs that expressed Kv4.2 channels tended to be more sensitive to BaCl2 blockade than RGCs without Kv4.2. In addition, BaCl2 decreased firing frequencies. To determine how Kv4.2 channels are regulated, the effect of bath application of the general dopamine agonist, ADTN, was determined. ADTN decreased IA current density, but increased firing rates.
The effect of BaCl2 on firing rates suggests Kv4.2-mediated currents regulate the action potential output in some RGCs. The unexpected result that ADTN decreased IA current density, but increased firing rates suggests that ADTN mediates more than just IA in RGCs. This is consistent with other known effects of dopamine in the retina.
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