Kv3-Like Potassium Channels Are Required for Sustained High-Frequency Firing in Basal Ganglia Output Neurons

Ding S, Matta SG, Zhou FM. Kv3-like potassium channels are required for sustained high-frequency firing in basal ganglia output neurons. J Neurophysiol 105: 554-570, 2011. First published December 15, 2010; doi:10.1152/jn.00707.2010. The GABA projection neurons in the substantial nigra pars reticulata (SNr) are key output neurons of the basal ganglia motor control circuit. These neurons fire sustained high-frequency, short-duration spikes that provide a tonic inhibition to their targets and are critical to movement control. We hypothesized that a robust voltage-activated K+ conductance that activates quickly and resists inactivation is essential to the remarkable fast-spiking capability in these neurons. Semi-quantitative RT-PCR (qRT-PCR) analysis on laser capture-microdissected nigral neurons indicated that mRNAs for Kv3.1 and Kv3.4, two key subunits for forming high activation threshold, fast-activating, slow-inactivating, 1 mM tetraethylammonium (TEA)-sensitive, fast delayed rectifier (IDR-fast) type Kv channels, are more abundant in fast-spiking SNr GABA neurons than in slow-spiking nigral dopamine neurons. Nucleated patch clamp recordings showed that SNr GABA neurons have a strong Kv3-like IDR-fast current sensitive to 1 mM TEA that activates quickly at depolarized membrane potentials and is resistant to inactivation. IDR-fast is smaller in nigral dopamine neurons. Pharmacological blockade of IDR-fast by 1 mM TEA impaired the high-frequency firing capability in SNr GABA neurons. Taken together, these results indicate that Kv3-like channels mediating fast-activating, inactivation-resistant IDR-fast current are critical to the sustained high-frequency firing in SNr GABA projection neurons and hence movement control.