title: Kv3-like potassium channels are required for sustained high-frequency firing in basal ganglia output neurons.
abstract: 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 (I(DR-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 I(DR-fast) current sensitive to 1 mM TEA that activates quickly at depolarized membrane potentials and is resistant to inactivation. I(DR-fast) is smaller in nigral dopamine neurons. Pharmacological blockade of I(DR-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 I(DR-fast) current are critical to the sustained high-frequency firing in SNr GABA projection neurons and hence movement control.
authors.affiliation: Department of Pharmacology, University of Tennessee College of Medicine, Memphis, TN 38163, USA.
authors.forename: Shengyuan
authors.initials: S
authors.lastname: Ding
authors.forename: Shannon G
authors.initials: SG
authors.lastname: Matta
authors.forename: Fu-Ming
authors.initials: FM
authors.lastname: Zhou
mesh_terms: D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D001479:Basal Ganglia / Q000502:physiology*; D001683:Biological Clocks / Q000502:physiology*; D005260:Female; D015640:Ion Channel Gating / Q000502:physiology; D008297:Male; D009046:Motor Neurons / Q000502:physiology*; D009068:Movement / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D051670:Shaw Potassium Channels / Q000502:physiology*
chemical_list: D051670:Shaw Potassium Channels