A transient receptor potential channel regulates basal ganglia output.
The substantia nigra pars reticulata (SNr) is a key basal ganglia output nucleus critical for movement control. A hallmark of the SNr gamma-aminobutyric acid (GABA)-containing projection neurons is their depolarized membrane potential, accompanied by rapid spontaneous spikes. Parkinsonian movement disorders are often associated with abnormalities in SNr GABA neuron firing intensity and/or pattern. A fundamental question is the molecular identity of the ion channels that drive these neurons to a depolarized membrane potential. Recent data show that SNr GABA projection neurons selectively express type 3 canonical transient receptor potential (TRPC3) channels. Such channels are tonically active and mediate an inward, Na(+)-dependent current, leading to a substantial depolarization and ensuring appropriate firing intensity and pattern in SNr GABA projection neurons. Equally important, TRPC3 channels in SNr GABA neurons are up-regulated by dopamine (DA) released from neighboring nigral DA neuron dendrites. Co-activation of D1 and D5 DA receptors leads to a TRPC3 channel-mediated inward current and increased firing in SNr GABA neurons, whereas D1-like receptor blockade reduces SNr GABA neuron firing frequency and increases their firing irregularity. TRPC3 channels serve as the effector channels mediating an ultra-short SNc-->SNr DA pathway that regulates the firing intensity and pattern of the basal ganglia output neurons.
Zhou
Fu-Ming
FM
Department of Pharmacology, University of Tennessee College of Medicine, Memphis TN 38163, USA. fzhou3@uthsc.edu
D000818:Animals; D001479:Basal Ganglia / Q000166:cytology / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism; D008954:Models, Biological; D009434:Neural Pathways / Q000378:metabolism; D009474:Neurons / Q000502:physiology*; D050051:Transient Receptor Potential Channels / Q000235:genetics / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D050051:Transient Receptor Potential Channels; D005680:gamma-Aminobutyric Acid; D004298:Dopamine