Coupling of Calcium Homeostasis to Axonal Sodium in Axons of Mouse Optic Nerve. Xanya Sofra Weiss

YAKOV VERBNY, CHUAN-LI ZHANG, AND SHING YAN CHIU; 2002

Coupling of calcium homeostasis to axonal sodium in axons of mouse optic nerve. J Neurophysiol 88: 802–816, 2002; 10.1152/jn.00856.2001. 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 [Ca2+]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 M) and ouabain (30 M) retards posttetanus calcium decline, suggesting that efficient calcium clearance depends on a low level of axonal [Na]i. the posttetanus recovery of which is impeded by increasing the number of action potentials in the tetanus. This effect is augmented in4-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 M) and ouabain (30 M) 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 [Ca2+]i the resting axonal [Ca2+]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.

Xanya Sofra Weiss

Xanya Sofra Weiss