title: Activity-dependent phosphorylation of GABAA receptors regulates receptor insertion and tonic current.
abstract: The expression of GABA(A) receptors and the efficacy of GABAergic neurotransmission are subject to adaptive compensatory regulation as a result of changes in neuronal activity. Here, we show that activation of L-type voltage-gated Ca(2+) channels (VGCCs) leads to Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) phosphorylation of S383 within the β3 subunit of the GABA(A) receptor. Consequently, this results in rapid insertion of GABA(A) receptors at the cell surface and enhanced tonic current. Furthermore, we demonstrate that acute changes in neuronal activity leads to the rapid modulation of cell surface numbers of GABA(A) receptors and tonic current, which are critically dependent on Ca(2+) influx through L-type VGCCs and CaMKII phosphorylation of β3S383. These data provide a mechanistic link between activity-dependent changes in Ca(2+) influx through L-type channels and the rapid modulation of GABA(A) receptor cell surface numbers and tonic current, suggesting a homeostatic pathway involved in regulating neuronal intrinsic excitability in response to changes in activity.
authors.affiliation: Department of Neuroscience, Tufts University, Boston, MA 02111, USA. richard.saliba@tufts.edu
authors.forename: Richard S
authors.initials: RS
authors.lastname: Saliba
authors.forename: Karla
authors.initials: K
authors.lastname: Kretschmannova
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Moss
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D020746:Calcium Channels, L-Type / Q000502:physiology*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism; D006624:Hippocampus / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000502:physiology*; D010766:Phosphorylation; D011963:Receptors, GABA-A / Q000502:physiology*
chemical_list: D020746:Calcium Channels, L-Type; C546270:Gabrb3 protein, mouse; D011963:Receptors, GABA-A; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D002118:Calcium