EFFECT OF QUIN-2 ON CA-45(2+) UPTAKE MEDIATED BY NA+I/CA-2+O EXCHANGE AND CA-45(2+) EFFLUX IN RAT-BRAIN SYNAPTOSOMES - A REQUIREMENT FOR [CA-2+]I

The Na+ Ca2+ exchanger of squid axons, barnacle muscle and sarcolemma requires micromolar intracellular calcium for activation in the Na+i Ca2+o exchange mode ('reverse' Na+ Ca2+ exchange). The requirement for [Ca2+]i has been demonstrated with the use of intracellular calcium buffers, such as Quin-2, to inhibit Na+i Ca2+o exchange. However, the inhibition of Na+i Ca2+o exchange in mammalian nerve terminals loaded with Quin-2 has not been observed [7], suggesting a lower sensitivity to low [Ca2+]i for this system. In contrast, the results reported herein indicate that 45Ca2+ uptake in synaptosomes through Na+i Ca2+o exchange is inhibited by Quin-2 much in the same way as it is in the squid, provided that synaptosomes are preincubated in low Ca2+ medium to avoid saturation of Quin-2. Under these conditions, 45Ca2+ efflux via Ca2+i Ca2+o exchange is also inhibited. Our results indicate that the Na+i Ca2+o and Ca2+i Ca2+o modes of the Na+ Ca2+ exchanger from rat brain synaptosomes require intracellular calcium for activation. However, because no clear relationship between the observed [Ca2+]i values and the inhibition of Na+i Ca2+o exchange has been found, it is suggested that localised submembrane calcium concentrations not detected by the [Ca2+]i probe might regulate the exchanger. © 1990.