title: Developmental upregulation of presynaptic NCKX underlies the decrease of mitochondria-dependent posttetanic potentiation at the rat calyx of Held synapse.
abstract: The sensitivity of posttetanic potentiation (PTP) to high-frequency stimulation (HFS) steeply decays during the first 2 postnatal weeks. We investigated the underlying mechanisms for the developmental change of PTP induced by HFS (100 Hz, 2 s) at postnatal days 4-6 and 9-11 at the rat calyx of Held synapse. Low-concentration tetraphenylphosphonium (2 μM), an inhibitor of mitochondrial Na(+)/Ca(2+) exchanger, suppressed the amount of posttetanic residual Ca(2+) and PTP to a larger extent at the immature calyx synapse, indicating a developmental reduction of mitochondrial contribution to PTP. The higher amount of mitochondrial Ca(2+) uptake during HFS and consequent posttetanic residual Ca(2+) at the immature calyx of Held was associated with higher peak of HFS-induced Ca(2+) transients, most likely because the mitochondrial Ca(2+) uptake during HFS was supralinearly dependent on the presynaptic resting Ca(2+) level. Probing into the contribution of Na(+)/Ca(2+) exchangers to Ca(2+) clearance, we found a specific upregulation of the K(+)-dependent Na(+)/Ca(2+) exchanger (NCKX) activity in the mature calyx of Held. We conclude that the upregulation of NCKX limits the Ca(2+) buildup and inhibits mitochondrial Ca(2+) uptake during HFS, which in turn results in the reduction of posttetanic residual Ca(2+) and PTP at the mature calyx of Held synapse.
authors.affiliation: Cell Physiology Laboratory, Department of Physiology and bioMembrane Plasticity Research Center, Seoul National University College of Medicine and Neuroscience Research Institute, Seoul National University Medical Research Center, Seoul, Republic of Korea.
authors.forename: Jae Sung
authors.initials: JS
authors.lastname: Lee
authors.forename: Myoung-Hwan
authors.initials: MH
authors.lastname: Kim
authors.forename: Won-Kyung
authors.initials: WK
authors.lastname: Ho
authors.forename: Suk-Ho
authors.initials: SH
authors.lastname: Lee
mesh_terms: D000200:Action Potentials; D000818:Animals; D001933:Brain Stem / Q000166:cytology / Q000254:growth & development / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling; D008928:Mitochondria / Q000378:metabolism*; D009861:Onium Compounds / Q000494:pharmacology; D009943:Organophosphorus Compounds / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D019831:Sodium-Calcium Exchanger / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism*; D009435:Synaptic Transmission; D015854:Up-Regulation
chemical_list: D009861:Onium Compounds; D009943:Organophosphorus Compounds; D019831:Sodium-Calcium Exchanger; C074530:potassium-dependent sodium-calcium exchanger; D002118:Calcium; C013289:tetraphenylphosphonium