title: Coupling of calcium homeostasis to axonal sodium in axons of mouse optic nerve.
abstract: Axonal populations in neonatal and mature optic nerves were selectively stained with calcium dyes for analysis of calcium homeostasis and its possible coupling to axonal Na. Repetitive nerve stimulation causes a rise in axonal [Ca(2+)](i) the posttetanus recovery of which is impeded by increasing the number of action potentials in the tetanus. This effect is augmented in 4-aminopyridine (4-AP; 1 mM), which dramatically increases the calcium and presumably sodium load during the tetanus. Increasing axonal [Na](i) with the Na-ionophore monensin (4-50 microM) and ouabain (30 microM) retards posttetanus calcium decline, suggesting that efficient calcium clearance depends on a low level of axonal [Na](i). Posttetanus calcium clearance is not affected by K-mediated depolarization. To further examine coupling between axonal [Na](i) and [Ca(2+)](i), the resting axonal [Ca(2+)](i) was monitored as axonal [Na(+)](i) was elevated with ouabain, veratridine, and monensin. In all cases, elevation of axonal [Na(+)](i) evokes a calcium influx into axons. This influx is unrelated to activation of calcium channels but is consistent with calcium influx via reversal of the Na/Ca exchanger expected as a consequence of axonal [Na(+)](i) elevation. In conclusion, this study demonstrates that calcium homeostasis in the axons of the optic nerve is strongly coupled to axonal [Na(+)](i) in a manner consistent with the Na/Ca exchanger playing a major role in extruding calcium following nerve activity.
authors.affiliation: Department of Physiology, University of Wisconsin School of Medicine, Madison 53706, USA.
authors.forename: Yakov
authors.initials: Y
authors.lastname: Verbny
authors.forename: Chuan-Li
authors.initials: CL
authors.lastname: Zhang
authors.forename: Shing Yan
authors.initials: SY
authors.lastname: Chiu
mesh_terms: D015761:4-Aminopyridine / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects; D000241:Adenosine / Q000494:pharmacology; D000375:Aging; D000818:Animals; D000831:Animals, Newborn; D001369:Axons / Q000187:drug effects / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone / Q000494:pharmacology; D004558:Electric Stimulation; D004594:Electrophysiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005456:Fluorescent Dyes; D006706:Homeostasis / Q000187:drug effects; D007476:Ionophores / Q000494:pharmacology; D051379:Mice; D008985:Monensin / Q000494:pharmacology; D009900:Optic Nerve / Q000187:drug effects / Q000378:metabolism*; D010042:Ouabain / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D012964:Sodium / Q000378:metabolism*; D019831:Sodium-Calcium Exchanger / Q000494:pharmacology; D014701:Veratridine / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D005456:Fluorescent Dyes; D007476:Ionophores; D026902:Potassium Channel Blockers; D019831:Sodium-Calcium Exchanger; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone; D010042:Ouabain; D014701:Veratridine; D008985:Monensin; D012964:Sodium; D015761:4-Aminopyridine; D000241:Adenosine; D002118:Calcium