|ZFIN ID: ZDB-PUB-081031-8|
Characterization of zebrafish (Danio rerio) NCX4: a novel NCX with distinct electrophysiological properties
On, C., Marshall, C.R., Perry, S.F., Le, H.D., Yurkov, V., Omelchenko, A., Hnatowich, M., Hryshko, L.V., and Tibbits, G.F.
|Source:||American journal of physiology. Cell physiology 296(1): C173-C181 (Journal)|
|Registered Authors:||Perry, Steve F.|
|PubMed:||18971388 Full text @ Am. J. Physiol. Cell Physiol.|
On, C., Marshall, C.R., Perry, S.F., Le, H.D., Yurkov, V., Omelchenko, A., Hnatowich, M., Hryshko, L.V., and Tibbits, G.F. (2009) Characterization of zebrafish (Danio rerio) NCX4: a novel NCX with distinct electrophysiological properties. American journal of physiology. Cell physiology. 296(1):C173-C181.
ABSTRACTMembers of the Na(+)-Ca(2+) exchanger (NCX) family are important regulators of cytosolic Ca(2+) in myriad tissues and are highly conserved across a wide range of species. Three distinct NCX genes and numerous splice variants exist in mammals, many of which have been characterized in a variety of heterologous expression systems. Recently, however, we discovered a fourth NCX gene (NCX4) which is found exclusively in teleost, amphibian and reptilian genomes. The zebrafish (Danio rerio) NCX4alpha encodes for a protein of 939 amino acids and shows a high degree of identity with known Na(+)-Ca(2+) exchangers. Although knock down of NCX4a activity in zebrafish embryos has been shown to alter left-right patterning, it has not been demonstrated that NCX4a functions as a Na(+)/Ca(2+) exchanger. In this study, we: 1) demonstrate for the first time that this gene encodes for a novel NCX; 2) characterize the tissue distribution of zebrafish NCX4a and 3) evaluate its kinetic and transport properties. While ubiquitously expressed, the highest levels of NCX4alpha expression occur in the brain and eyes. NCX4a exhibits modest levels of Na(+)-dependent inactivation and requires much higher levels of regulatory Ca(2+) to activate outward exchange currents. NCX4a also exhibited extremely fast recovery from Na(+)-dependent inactivation of outward currents, faster than any previously characterized wild-type exchanger. While this result suggests that the I1 inactive state of NCX4a is far less stable than in other NCX family members, this exchanger was still strongly inhibited by 2 microM XIP (eXchanger Inhibitory Peptide). We have demonstrated that a new putative member of the NCX gene family NCX4a encodes for a Na(+)/Ca(2+) exchanger with unique properties including an extremely rapid recovery from Na(+)-dependent inactivation. These data will be useful in understanding the role that NCX4a plays in embryological development as well as in the adult where it is expressed ubiquitously. Key words: calcium homeostasis, NCX, development.