Constitutively active TRPC3 channels regulate basal ganglia output neurons.
A hallmark of the GABA projection neurons of the substantia nigra pars reticulata (SNr), a key basal ganglia output nucleus, is its depolarized membrane potential and rapid spontaneous spikes that encode the basal ganglia output. Parkinsonian movement disorders are often associated with abnormalities in SNr GABA neuron firing intensity and/or pattern. A fundamental question remains regarding the molecular identity of the ion channels that drive these neurons to a depolarized membrane potential. We show here that SNr GABA projection neurons selectively express type 3 canonical transient receptor potential (TRPC3) channels. These channels are tonically active and mediate an inward, Na+-dependent current, leading to a substantial depolarization in these neurons. Inhibition of TRPC3 channels induces hyperpolarization, decreases firing frequency, and increases firing irregularity. These data demonstrate that TRPC3 channels play important roles in ensuring the appropriate firing intensity and pattern in SNr GABA projection neurons that are crucial to movement control.
Zhou
Fu-Wen
FW
Department of Pharmacology, University of Tennessee College of Medicine, Memphis, Tennessee 38163, USA.
Matta
Shannon G
SG
Zhou
Fu-Ming
FM
D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D000906:Antibodies / Q000494:pharmacology; D001479:Basal Ganglia / Q000166:cytology*; D002118:Calcium / Q000378:metabolism; D004558:Electric Stimulation / Q000379:methods; D005260:Female; D005439:Flufenamic Acid / Q000494:pharmacology; D005682:Gadolinium / Q000494:pharmacology; D005968:Glutamate Decarboxylase / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D051379:Mice; D008810:Mice, Inbred C57BL; D009475:Neurons, Afferent / Q000502:physiology*; D018408:Patch-Clamp Techniques / Q000379:methods; D012333:RNA, Messenger / Q000378:metabolism; D012964:Sodium / Q000378:metabolism; D050052:TRPC Cation Channels / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D000906:Antibodies; D012333:RNA, Messenger; D050052:TRPC Cation Channels; C104603:TRPC3 cation channel; D005439:Flufenamic Acid; D012964:Sodium; D005682:Gadolinium; D014446:Tyrosine 3-Monooxygenase; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1; C038958:gadolinium chloride; D002118:Calcium