Kv3-like potassium channels are required for sustained high-frequency firing in basal ganglia output neurons.
J Neurophysiol
; 105(2): 554-70, 2011 Feb.
Article
em En
| MEDLINE
| ID: mdl-21160004
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Gânglios da Base
/
Relógios Biológicos
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Potenciais de Ação
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Canais de Potássio Shaw
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Neurônios Motores
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Movimento
Limite:
Animals
Idioma:
En
Revista:
J Neurophysiol
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Estados Unidos