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

Abstract

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.

Target Cell-Specific Involvement of Presynaptic Mitochondria in Post-Tetanic Potentiation at Hippocampal Mossy Fiber Synapses

“…1 A, available at www.jneurosci.org as supplemental material). The increase in [OGB1] accompanied the decrease in the peak amplitude of AP-CaT and the increase in its decay time constant, indicative of increase in the Ca 2ϩ buffer concentration at the MFB (Neher and Augustine, 1992;Kim et al, 2003) (supplemental Fig. 1 B, available at www.jneurosci.org as supplemental material).…”

An Essential Role for the K+-dependent Na+/Ca2+-exchanger, NCKX4, in Melanocortin-4-receptor-dependent Satiety

“…Although ion channel activation is responsible for a rapid increase in Ca 2ϩ levels, longer term regulation of Ca 2ϩ depends mostly on extrusion pathways (2). Principal among these, particularly in neurons (3,4), is the family of K ϩ -dependent Na ϩ /Ca 2ϩ -exchangers (NCKX1 to -5), 2 encoded by the slc24 genes (5,6). NCKX family members are broadly expressed in various tissues, and particularly enriched in neurons of the brain.…”

Na+-dependent Inactivation of the Retinal Cone/Brain Na+/Ca2+-K+ Exchanger NCKX2

“…Inactivation of NCKX2 may be a useful regulatory mechanism that operates under physiological conditions. Mounting evidence points to NCKX2 being an important Ca 2ϩ clearance mechanism in neuronal synaptic terminals (13)(14)(15), which are specialized compartments that experience frequent and dynamic Ca 2ϩ fluxes and depolarized membrane potential resulting from frequent invasions of action potential spikes. Persistent presynaptic activity leads to persistent elevations in presynaptic terminal Ca 2ϩ concentrations (43,44), associated with an increase in intraterminal Na ϩ levels (up to peaks of 80 mM) (45).…”

“…The Na ϩ /Ca 2ϩ -K ϩ exchanger (NCKX) NCKX1 was first reported in retinal rod outer segments and is the isoform on which most extensive physiological studies have been performed (6 -8). NCKX2 transcripts have been reported in the brain and retina (9 -12), and recent emergent evidence indicates that this isoform is important for regulation of Ca 2ϩ levels in synaptic terminals (13)(14)(15). NCKX3 and NCKX4 transcripts are also found in the brain, but have also been localized to smooth muscle of the aorta, uterus, and intestine (16,17).…”