title: Transient Activation of GABAB Receptors Suppresses SK Channel Currents in Substantia Nigra Pars Compacta Dopaminergic Neurons.
abstract: Dopaminergic (DA) neurons in the substantia nigra pars compacta (SNc) are richly innervated by GABAergic neurons. The postsynaptic effects of GABA on SNc DA neurons are mediated by a mixture of GABAA and GABAB receptors. Although activation of GABAA receptors inhibits spike generation, the consequences of GABAB receptor activation are less well characterized. To help fill this gap, perforated patch recordings were made from young adult mouse SNc DA neurons. Sustained stimulation of GABAB receptors hyperpolarized SNc DA neurons, as previously described. However, transient stimulation of GABAB receptors by optical uncaging of GABA did not; rather, it reduced the opening of small-conductance, calcium-activated K+ (SK) channels and increased the irregularity of spiking. This modulation was attributable to inhibition of adenylyl cyclase and protein kinase A. Thus, because suppression of SK channel activity increases the probability of burst spiking, transient co-activation of GABAA and GABAB receptors could promote a pause-burst pattern of spiking.
authors.affiliation: Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States of America.
authors.forename: Chad M
authors.initials: CM
authors.lastname: Estep
authors.affiliation: Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States of America.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Galtieri
authors.affiliation: Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States of America.
authors.forename: Enrico
authors.initials: E
authors.lastname: Zampese
authors.affiliation: Department of Medical Neurobiology, Institute of Medical Research Israel-Canada, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel.
authors.forename: Joshua A
authors.initials: JA
authors.lastname: Goldberg
authors.affiliation: Laboratory of Molecular and Cellular Neuroscience, Rockefeller University, New York, NY, United States of America.
authors.forename: Lars
authors.initials: L
authors.lastname: Brichta
authors.affiliation: Laboratory of Molecular and Cellular Neuroscience, Rockefeller University, New York, NY, United States of America.
authors.forename: Paul
authors.initials: P
authors.lastname: Greengard
authors.affiliation: Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States of America.
authors.forename: D James
authors.initials: DJ
authors.lastname: Surmeier
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D059290:Dopaminergic Neurons / Q000378:metabolism*; D005260:Female; D059330:GABAergic Neurons / Q000378:metabolism; D015640:Ion Channel Gating / Q000187:drug effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D065842:Pars Compacta / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D011963:Receptors, GABA-A / Q000378:metabolism; D018080:Receptors, GABA-B / Q000378:metabolism*; D051640:Small-Conductance Calcium-Activated Potassium Channels / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
chemical_list: D011963:Receptors, GABA-A; D018080:Receptors, GABA-B; D051640:Small-Conductance Calcium-Activated Potassium Channels; D005680:gamma-Aminobutyric Acid; D017868:Cyclic AMP-Dependent Protein Kinases; D000262:Adenylyl Cyclases