J Neurophysiol (November 1, 2002). 10.1152/jn.00130.2002
Submitted on 21 February 2002
Accepted on 2 August 2002

Na⁺-Ca²⁺ Exchanger Controls the Gain of the Ca²⁺ Amplifier in the Dendrites of Amacrine Cells

Section of Neurobiology, Physiology and Behavior, Division of Biological Sciences, University of California, Davis, California 95616

Hurtado, Jose, Salvador Borges, and Martin Wilson. Na⁺-Ca²⁺ Exchanger Controls the Gain of the Ca²⁺ Amplifier in the Dendrites of Amacrine Cells. J. Neurophysiol. 88: 2765-2777, 2002. We have previously shown that disabling forward-mode Na⁺-Ca²⁺ exchange in amacrine cells greatly prolongs the depolarization-induced release of transmitter. To investigate the mechanism for this, we imaged [Ca²⁺]_i in segments of dendrites during depolarization. Removal of [Na⁺]_o produced no immediate effect on resting [Ca²⁺]_i but did prolong [Ca²⁺]_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 [Ca²⁺] over micrometer-length scales that collapsed once [Na⁺]_o was restored. Prolongation of [Ca²⁺]_i transients by removal of [Na⁺]_o is not due to reverse mode operation of Na⁺-Ca²⁺ exchange but is instead a consequence of Ca²⁺ release from endoplasmic reticulum (ER) stores over which Na⁺-Ca²⁺ exchange normally exercises control. Even in normal [Na⁺]_o, hotspots for [Ca²⁺] could be seen following depolarization, that are attributable to local Ca²⁺-induced Ca²⁺ release. Hotspots were seen to be labile, probably reflecting the state of local stores or their Ca²⁺ release channels. When ER stores were emptied of Ca²⁺ by thapsigargin, [Ca²⁺] transients in dendrites were greatly reduced and unaffected by the removal of [Na⁺]_o implying that even when Na⁺-Ca²⁺ exchange is working normally, the majority of the [Ca²⁺]_i increase by depolarization is due to internal release rather than influx across the plasma membrane. Na⁺-Ca²⁺ exchange has an important role in controlling [Ca²⁺] dynamics in amacrine cell dendrites chiefly by moderating the positive feedback of the Ca²⁺ amplifier.