Our goal is to elucidate the factors that regulate intracellular calcium in mammalian neurons (including nerve terminals) and astrocytes, and to determine how they influence physiological and pathophysiological processes. The Na/Ca exchange transport system, present in the plasmalemma of neurons and astrocytes, has the capacity to move large amounts of Ca2+ very quickly; it appears to play a dominant role in the extrusion of Ca2+ from these cells following activation. Therefore, much of the focus of this project is on the role played by the plasmalemmal Na/Ca exchanger in the brain: 1) its contribution to the control of intracellular free Ca2+ and stored Ca2+, 2) its influence on the responsiveness of neurons and astrocytes to depolarization, transmitters, and excitotoxins, and 3) its relationship to neuronal cell injury and death. To this end, the detailed kinetic properties (maximal flux rates, ion affinities, etc.) of the Na/Ca exchanger will be determined in rat forebrain nerve terminals (synaptosomes). These data will be compared to similar (but limited) data that will be obtained from bovine neurohypophyseal synaptosomes. Intra-terminal Ca2+ homeostasis in bovine neurohypophyseal synaptosomes will then be studied with the fluorescent indicators, fura-2 (for Ca2+) and SBFI (for Na+ measurements, related to Na/Ca exchange), using digital imaging methods. In parallel, fura-2 and SBFI will be used with digital imaging methods to examine the role of Na/Ca exchange in cultured rat striatal neurons and astrocytes to determine the role of the exchanger in regulating the responsiveness of these cells to neurotransmitters, hypoxia and excitotoxins. Finally, the investigators will employ a contribution of immunocytochemical methods with a polyclonal antibody to the exchanger, and in situ hybridization methods with a specific probe for the rat brain exchanger, to determine its distribution in the brain at various times during development and in the adult. The results of these studies should help us to understand the pathogenesis of (and perhaps develop new therapeutic strategies for) the altered cell Ca2+ metabolism that contributes to neuronal cell injury and cell death in a wide variety of neuronal diseases.
| Song, Hong; Karashima, Eiji; Hamlyn, John M et al. (2014) Ouabain-digoxin antagonism in rat arteries and neurones. J Physiol 592:941-69 |
| Song, Hong; Thompson, Scott M; Blaustein, Mordecai P (2013) Nanomolar ouabain augments Ca2+ signalling in rat hippocampal neurones and glia. J Physiol 591:1671-89 |
| Blaustein, Mordecai P (2013) Livin' with NCX and lovin' it: a 45 year romance. Adv Exp Med Biol 961:3-15 |
| Song, Hong; Lee, Moo Yeol; Kinsey, Stephen P et al. (2006) An N-terminal sequence targets and tethers Na+ pump alpha2 subunits to specialized plasma membrane microdomains. J Biol Chem 281:12929-40 |
| Lee, Moo Yeol; Song, Hong; Nakai, Junichi et al. (2006) Local subplasma membrane Ca2+ signals detected by a tethered Ca2+ sensor. Proc Natl Acad Sci U S A 103:13232-7 |
| Golovina, Vera A (2005) Visualization of localized store-operated calcium entry in mouse astrocytes. Close proximity to the endoplasmic reticulum. J Physiol 564:737-49 |
| Lencesova, Lubomira; O'Neill, Andrea; Resneck, Wendy G et al. (2004) Plasma membrane-cytoskeleton-endoplasmic reticulum complexes in neurons and astrocytes. J Biol Chem 279:2885-93 |
| Gonzalez-Serratos, Hugo; Chang, Ruzhang; Rozycka, Monika et al. (2003) Role of the T-system and the Na-K pump on fatigue development in phasic skeletal muscle. Adv Exp Med Biol 538:543-55; discussion 555 |
| Golovina, Vera A; Song, Hong; James, Paul F et al. (2003) Na+ pump alpha 2-subunit expression modulates Ca2+ signaling. Am J Physiol Cell Physiol 284:C475-86 |
| Blaustein, Mordecai P; Golovina, Vera A; Song, Hong et al. (2002) Organization of Ca2+ stores in vascular smooth muscle: functional implications. Novartis Found Symp 246:125-37; discussion 137-41, 221- |
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