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Agents that Promote Protein Phosphorylation Inhibit the Activity of the Na + /Ca 2+ Exchanger and Prolong Ca 2+ Transients in Bovine Chromaffin Cells
Author(s) -
Lin Lih Fang,
Kao LungSen,
Westhead Edward W.
Publication year - 1994
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1994.63051941.x
Subject(s) - okadaic acid , protein kinase c , sodium calcium exchanger , protein kinase a , phosphorylation , chromaffin cell , chemistry , calcium , protein phosphorylation , sodium–hydrogen antiporter , protein kinase inhibitor , biochemistry , biophysics , sodium , intracellular , biology , phosphatase , endocrinology , catecholamine , adrenal medulla , organic chemistry
The Na + /Ca 2+ exchanger is an important element in the maintenance of calcium homeostasis in bovine chromaffin cells. The Na + /Ca 2+ exchanger from other cell types has been extensively studied, but little is known about its regulation in the cell. We have investigated the role of reversible protein phosphorylation in the activity of the Na + /Ca 2+ exchanger of these cells. Cells treated with 1 m M dibutyryl cyclic AMP (dbcAMP), 1 µ M phorbol 12,13‐dibutyrate, 1 µ M okadaic acid, or 100 n M calyculin A showed lowered Na + /Ca 2+ exchange activity and prolonged cytosolic Ca 2+ transients caused by depolarization. A combination of 10 n M okadaic acid and 1 µ M dbcAMP synergistically inhibited Na + /Ca 2+ exchange activity. Conversely, 50 µ M 1‐(5‐isoquinolinylsulfonyl)‐2‐methylpiperazine, a protein kinase inhibitor, enhanced Na + /Ca 2+ exchange activity. Moreover, we used cyclic AMP‐dependent protein kinase and calcium phospholipid‐dependent protein kinase catalytic subunits to phosphorylate isolated membrane vesicles and found that the Na + /Ca 2+ exchange activity was inhibited by this treatment. These results indicate that reversible protein phosphorylation modulates the activity of the Na + /Ca 2+ exchanger and suggest that modulation of the exchanger may play a role in the regulation of secretion.