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Na + —Ca 2+ Exchange Currents in Cortical Neurons: Concomitant Forward and Reverse Operation and Effect of Glutamate
Author(s) -
Yu Shan Ping,
Choi Dennis W.
Publication year - 1997
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.1460-9568.1997.tb01482.x
Subject(s) - chemistry , biophysics , glutamate receptor , intracellular , membrane potential , biochemistry , receptor , biology
Na + ‐Ca 2+ exchanger‐associated membrane currents were studied in cultured murine neocortical neurons, using whole‐cell recording combined with intracellular perfusion. A net inward current specifically associated with forward (Na + o ‐Ca 2+ i ) exchange was evoked at ‐40 mV by switching external 140 mM Li + to 140 mM Na + . The voltage dependence of this current was consistent with that predicted for 3Na + :1Ca 2+ exchange. As expected, the current depended on internal Ca 2+ , and could be blocked by intracellular application of the exchanger inhibitory peptide, XIP. Raising internal Na + from 3 to 20 mM or switching the external solution from 140 mM Li + to 30 mM Na + activated outward currents, consistent with reverse (Na + ,‐Ca 2+ o ) exchange. An external Ca 2+ ‐sensitive current was also identified as associated with reverse Na + ‐Ca 2+ exchange based on its internal Na + dependence and sensitivity to XIP. Combined application of external Na + and Ca 2+ in the absence of internal Na + triggered a 3.3–fold larger inward current than the current activated in the presence of 3 mM internal Na + , raising the intriguing possibility that Na + ‐Ca 2+ exchangers might concurrently operate in both the forward and the reverse direction, perhaps in different subcellular locations. With this idea in mind, we examined the effect of excitotoxic glutamate receptor activation on exchanger operation. After 3–5 min of exposure to 100–200 μM glutamate, the forward exchanger current was significantly increased even when external Na + was reduced to 100 mM, and the external Ca 2+ ‐activated reverse exchanger current was eliminated.