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The Journal of Neuroscience, December 17, 2003, 23(37):11673-11680

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Cellular/Molecular
Distribution of K⁺-Dependent Na⁺/Ca²⁺ Exchangers in the Rat Supraoptic Magnocellular Neuron Is Polarized to Axon Terminals

Myoung-Hwan Kim,¹ Sang-hyuk Lee,² Kyeong Han Park,² Won-Kyung Ho,¹ and Suk-Ho Lee¹

Departments of ¹Physiology and ²Anatomy, Seoul National University College of Medicine, Chongno-Ku, Seoul, 110-799, Korea

Neurons are polarized into compartments such as the soma, dendrites, and axon terminals, each of which has highly specialized functions. To test whether Ca²⁺ is differently handled in different compartments of a neuron, we investigated Ca²⁺ clearance mechanisms in somata of supraoptic magnocellular neurosecretory cells (MNCs) and in their axon terminals located in neurohypophyses. Using patch-clamp and microfluorometry techniques, Ca²⁺ transients were evoked by depolarizing pulses. Endogenous Ca²⁺ binding ratios (_S) and Ca²⁺ clearance rates were calculated from the decay phases of Ca²⁺ transients according to the single compartment model. Mean values of _S were 79 ± 2.6 in somata of MNCs and 187 ± 19 in axon terminals. Ca²⁺ clearance rate in axon terminals, which were calculated from time derivative of Ca²⁺ decay and the _S values, were approximately threefold higher than in somata. In response to external Na⁺ reduction, Ca²⁺ clearance rates were reduced by 65% in axon terminals, but did not change in somata. Immunohistochemical assays confirmed that K⁺-dependent Na⁺/Ca²⁺ exchanger (NCKX2) was specifically localized to neurohypophysial axon terminals and was not found in somata. In somata, inhibition of sarcoendoplasmic reticulum Ca²⁺-ATPase (SERCA) pumps, mitochondrial Ca²⁺-uniporter, and plasma membrane Ca²⁺-ATPase (PMCA) pumps decreased Ca²⁺ clearance rate by 48, 27, and 21%, respectively. These results suggest that neurohypophysial axon terminals have greater Ca²⁺ clearance power than somata because of the specific localization of NCKX2, and that Ca²⁺ clearance in somata of MNCs is mediated by SERCA pumps, mitochondrial uniporter, and PMCA pumps.

Key words: calcium clearance; supraoptic nucleus; neurohypophysis; NCKX; SERCA; mitochondria

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Received July 25, 2003; revised October 24, 2003; accepted October 28, 2003.

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