title: Na+/Ca2+ exchange and Ca2+ homeostasis in axon terminals of mammalian central neurons.
abstract: We investigated Ca2+ clearance mechanisms (CCMs) at the axon terminals of mammalian central neurons: neurohypophysial (NHP) axon terminals and calyces of Held. Ca2+ transients were evoked by applying a short depolarization pulse via a patch pipette containing Ca2+ indicator dye. Quantitative analysis of the Ca2+ decay phases revealed that Na+/Ca2+ exchange (Na/CaX) is a major CCM at both axon terminals. In contrast, no Na/CaX activity was found in the somata of NHP axon terminals (supraoptic magnocellular neurons), indicating that the distribution of Na+/Ca2+ exchangers is polarized. Intracellular dialysis of axon terminals with a K+-free pipette solution attenuated the Na/CaX activities by 90% in the NHP axon terminals and by 60% at the calyx of Held, indicating that K+-dependent Na+/Ca2+ exchangers are involved. Studying the effects of specific inhibitors of smooth endoplasmic reticulum Ca2+-ATPase (SERCA) and plasma membrane Ca2+-ATPase (PMCA) on the Ca2+ decay rate revealed that PMCA contributed 23% of total Ca2+ clearance, but that SERCA made no contribution at the calyx of Held. The contribution of mitochondria was negligible for small Ca2+ transients, but became apparent at peak Ca2+ levels higher than 2.5 microM. When mitochondrial function was inhibited, the dependence of CCMs on [Ca2+]i at the calyx of Held showed saturation kinetics with K(1/2) = 1.7 microM, suggesting that the Na/CaX activity is saturated at high [Ca2+]i. The presynaptic Na+/Ca2+ exchanger activity, which competes for cytosolic Ca2+ with mitochondria, may contribute to nonplastic synaptic transmission at these axon terminals.
authors: National Research Laboratory for Cell Physiology, Department of Physiology, Seoul National University College of Medicine, Chongno-Ku, Seoul 110-799, South Korea. leesukho@snu.ac.kr
authors: Suk-Ho
authors: SH
authors: Lee
authors: Myoung-Hwan
authors: MH
authors: Kim
authors: Ju-Young
authors: JY
authors: Lee
authors: Sang Hun
authors: SH
authors: Lee
authors: Doyun
authors: D
authors: Lee
authors: Kyeong Han
authors: KH
authors: Park
authors: Won-Kyung
authors: WK
authors: Ho
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D006706:Homeostasis; D008322:Mammals; D008928:Mitochondria / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D011188:Potassium / Q000378:metabolism; D017729:Presynaptic Terminals / Q000378:metabolism; D019831:Sodium-Calcium Exchanger / Q000378:metabolism*
chemical_list: D019831:Sodium-Calcium Exchanger; D011188:Potassium; D002118:Calcium