Role of sodium-calcium exchange in regulation of intracellular calcium in nerve terminals

Abstract

Ca efflux from rat brain presynaptic nerve terminals (synaptosomes) was examined after loading the terminals with 45Ca during a brief depolarization, usually in media containing 20 microM Ca labeled with 45Ca, to assure a small (physiological) load. Efflux of 45Ca was very slow in the absence of external Na and Ca (approximately 0.5% of the load/s) and was greatly accelerated by Na and/or Ca (presumably Na+-Ca2+ and Ca2+-Ca2+ exchange, respectively). The dependence of 45Ca efflux on external Na was sigmoid, with a Hill coefficient of approximately 2.5; this implies that more than two external Na ions are required to activate the efflux of one Ca ion. The external Na (Nao)-dependent Ca efflux was inhibited by 1 mM external La, by low temperature (Q10 congruent to 2.3), and by raising external K (to depolarize the synaptosomes). With small Ca loads, the mitochondrial uncoupler, carbonyl cyanide-p-trifluoromethoxyphenylhydrazone (FCCP), had negligible effect on either Ca uptake or efflux; with large loads (greater than or equal to 5 nmol/mg protein), however, FCCP reduced the depolarization-stimulated Ca uptake and increased the Nao-dependent Ca efflux. These effects may be attributed to reduction of mitochondrial Ca sequestration. Mitochondria do not appear to sequester much Ca when the loads are smaller (and more physiological). Estimations of Ca efflux indicate that approximately 20% of a small 45Ca load (approximately 0.75 nmol Ca/mg protein) may be extruded via Na+-Ca2+ exchange within 1 s; this corresponds to a net Ca efflux of approximately 110 pmol Ca X mg protein-1 X s-1.(ABSTRACT TRUNCATED AT 250 WORDS)

Interplay between Na+/Ca2+ Exchangers and Mitochondria in Ca2+ Clearance at the Calyx of Held

“…In neuronal compartments with a high surface-to-volume ratio, CCMs in the plasma membrane may clear cytosolic Ca 2ϩ more efficiently than other CCMs that sequestrate Ca 2ϩ into intracellular organelles. Various axon terminals effectively clear Ca 2ϩ using plasma membrane CCMs such as Na/CaX and PMCA (Gill et al, 1981;Sanchez-Armass and Blaustein, 1987;Reuter et al, 1995;Morgans et al, 1998;Zenisek et al, 2000;Chuhma and Ohmori, 2002;Lee et al, 2002). Our results indicate that Na/CaX is a primary CCM at the calyx of Held.…”

Involvement of Na+-Ca2+Exchanger in Intracellular Ca2+Increase and Neuronal Injury Induced by Polychlorinated Biphenyls in Human Neuroblastoma SH-SY5Y Cells

“…To clarify whether NCX is effectively involved in A1254-induced [Ca 2ϩ ] i increase, the pattern of the expression of the three known NCX isoforms NCX1, NCX2 and NCX3 was first characterized in SH-SY5Y cells by RT-PCR analy- Inglefield and Shafer (2000), with a consequent opening of Na ϩ -sensitive voltage channels. This event leads to an increase of intracellular Na ϩ ion concentration, which in turn may force the NCX to work in the reverse mode (Baker and McNaughton, 1976;DiPolo, 1979;Sanchez-Armass and Blaustein, 1987;Annunziato et al, 2004). This chain of events seems to be supported by the results showing that tetrodotoxin, a well known blocker of fast-activated Na ϩ channels (Almers and Levinson, 1975;Weiser and Wilson, 2002), prevents Ca 2ϩ oscillations evoked by A1254 in developing cortical neurons (Inglefield and Shafer, 2000).…”

“…In addition, it has been reported that PCBs can also perturb Ca 2ϩ homeostasis by acting on ryanodine (Wong and Pessah, 1996;Mundy et al, 1999) and inositol 1,4,5-triphosphate receptorsensitive Ca 2ϩ release (Inglefield et al, 2001). The Na ϩ -Ca 2ϩ exchanger (NCX) is a plasmamembrane exchanger mainly involved in the maintenance of cytosolic Ca 2ϩ homeostasis (Sanchez-Armass and Blaustein, 1987). This antiporter couples the uphill extrusion of Ca 2ϩ to the entrance of Na ϩ into the cell (forward mode) and down its electrochemical gradient.…”

Nitric Oxide Stimulates NCX1 and NCX2 but Inhibits NCX3 Isoform by Three Distinct Molecular Determinants

“…Complex patterns regulate the specificity of Ca 2ϩ signaling through the activity of plasma membrane channels and transporters, including the Na ϩ /Ca 2ϩ exchanger (NCX). For instance, this bidirectional high-capacity and low-affinity ionic transporter, by exchanging three Na ϩ ions for one Ca 2ϩ ion (Sanchez-Armass and Blaustein, 1987;Annunziato et al, 2004), plays a relevant role in maintaining intracellular free Ca 2ϩ homeostasis. Three different gene products of NCX have been cloned (Nicoll et al, 1990(Nicoll et al, , 1996Li et al, 1994): NCX1, which is the only isoform expressed in the heart and is ubiquitously expressed in several tissues, and NCX2 and NCX3, which are widely expressed in the brain (Papa et al, 2003) and in the skeletal muscle (Lee et al, 1994).…”