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

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 (kappaS) and Ca2+ clearance rates were calculated from the decay phases of Ca2+ transients according to the single compartment model. Mean values of kappaS 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 kappaS 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.