RT Journal Article
SR Electronic
T1 K+-Dependent Na+/Ca2+Exchange Is a Major Ca2+ Clearance Mechanism in Axon Terminals of Rat Neurohypophysis
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 6891
OP 6899
DO 10.1523/JNEUROSCI.22-16-06891.2002
VO 22
IS 16
A1 Lee, Suk-Ho
A1 Kim, Myoung-Hwan
A1 Park, Kyeong Han
A1 Earm, Yung E.
A1 Ho, Won-Kyung
YR 2002
UL http://www.jneurosci.org/content/22/16/6891.abstract
AB Two different families of Na+/Ca2+ exchangers, K+-independent NCX and K+-dependent NCKX, are known. Exploiting the outward K+ gradient, NCKX is able to extrude Ca2+ more efficiently than NCX, even when the Na+ gradient is reduced. The NCKX, which was originally thought to be limited to the retinal photoreceptor, was shown recently to be widely distributed in the brain. We investigated the contribution of Na+/Ca2+exchange to Ca2+ clearance mechanisms in neurohypophysial (NHP) axon terminals, using patch-clamp and microfluorometry techniques. In the presence of internal K+, Ca2+ decay was significantly slowed by the removal of external Na+, indicative of the role of Na+/Ca2+ exchange. As internal [K+] was decreased, Ca2+ decay rate and its dependence on Na+ were greatly attenuated. In the absence of internal K+, Ca2+ decay rate was little affected by Na+ removal. Quantitative analysis using Ca2+ decay rate constant indicated that >60% of Ca2+ extrusion is mediated by Na+/Ca2+ exchange when peak [Ca2+] level is higher than 500 nm, and ∼90% of Na+/Ca2+ exchange activity is K+ dependent. In situhybridization confirmed the expression of NCKX2 transcripts in the supraoptic nucleus in which soma of NHP axon terminals are located. To our knowledge, this is the first report to show the significant role of K+-dependent Na+/Ca2+ exchange in neuronal cells other than photoreceptors. Considering that axon terminals are subject to an invasion by high-frequency Na+ spikes, which may lower Na+ gradients, the presence of NCKX may have a functional significance in intracellular Ca2+ regulation.