title: Calcium-dependent isoforms of protein kinase C mediate glycine-induced synaptic enhancement at the calyx of Held.
abstract: Depolarization of presynaptic terminals that arises from activation of presynaptic ionotropic receptors, or somatic depolarization, can enhance neurotransmitter release; however, the molecular mechanisms mediating this plasticity are not known. Here we investigate the mechanism of this enhancement at the calyx of Held synapse, in which presynaptic glycine receptors depolarize presynaptic terminals, elevate resting calcium levels, and potentiate release. Using knock-out mice of the calcium-sensitive PKC isoforms (PKC(Ca)), we find that enhancement of evoked but not spontaneous synaptic transmission by glycine is mediated primarily by PKC(Ca). Measurements of calcium at the calyx of Held indicate that deficits in synaptic modulation in PKC(Ca) knock-out mice occur downstream of presynaptic calcium increases. Glycine enhances synaptic transmission primarily by increasing the effective size of the pool of readily releasable vesicles. Our results reveal that PKC(Ca) can enhance evoked neurotransmitter release in response to calcium increases caused by small presynaptic depolarizations.
authors.affiliation: Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: YunXiang
authors.initials: Y
authors.lastname: Chu
authors.forename: Diasynou
authors.initials: D
authors.lastname: Fioravante
authors.forename: Monica
authors.initials: M
authors.lastname: Thanawala
authors.forename: Michael
authors.initials: M
authors.lastname: Leitges
authors.forename: Wade G
authors.initials: WG
authors.lastname: Regehr
mesh_terms: D000818:Animals; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D017626:Cochlear Nucleus / Q000201:enzymology* / Q000502:physiology / Q000648:ultrastructure; D004558:Electric Stimulation; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D005260:Female; D005998:Glycine / Q000494:pharmacology*; D017774:Long-Term Potentiation / Q000187:drug effects*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000502:physiology*; D017729:Presynaptic Terminals / Q000187:drug effects / Q000502:physiology; D011493:Protein Kinase C / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D064546:Protein Kinase C beta; D051571:Protein Kinase C-alpha / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D013331:Strychnine / Q000494:pharmacology; D013569:Synapses / Q000187:drug effects / Q000201:enzymology* / Q000502:physiology
chemical_list: D009419:Nerve Tissue Proteins; D011493:Protein Kinase C; D064546:Protein Kinase C beta; D051571:Protein Kinase C-alpha; D013331:Strychnine; D005998:Glycine