Na -Ca Exchanger Controls the Gain of the Ca Amplifier in the Dendrites of Amacrine Cells

Hurtado, Jose, Salvador Borges, and Martin Wilson. Na -Ca exchanger controls the gain of the Ca amplifier in the dendrites of amacrine cells J Neurophysiol 88: 2765–2777, 2002; 10.1152/jn.00130.2002. We have previously shown that disabling forward-mode Na -Ca exchange in amacrine cells greatly prolongs the depolarization-induced release of transmitter. To investigate the mechanism for this, we imaged [Ca ]i in segments of dendrites during depolarization. Removal of [Na ]o produced no immediate effect on resting [Ca ]i but did prolong [Ca 2 ]i transients induced by brief depolarization in both voltage-clamped and unclamped cells. In some cells, depolarization gave rise to stable patterns of higher and lower [Ca ] over micrometer-length scales that collapsed once [Na ]o was restored. Prolongation of [Ca 2 ]i transients by removal of [Na ]o is not due to reverse mode operation of Na -Ca exchange but is instead a consequence of Ca release from endoplasmic reticulum (ER) stores over which Na -Ca exchange normally exercises control. Even in normal [Na ]o, hotspots for [Ca 2 ] could be seen following depolarization, that are attributable to local Ca -induced Ca release. Hotspots were seen to be labile, probably reflecting the state of local stores or their Ca release channels. When ER stores were emptied of Ca by thapsigargin, [Ca ] transients in dendrites were greatly reduced and unaffected by the removal of [Na ]o implying that even when Na -Ca exchange is working normally, the majority of the [Ca ]i increase by depolarization is due to internal release rather than influx across the plasma membrane. Na -Ca exchange has an important role in controlling [Ca ] dynamics in amacrine cell dendrites chiefly by moderating the positive feedback of the Ca amplifier.