%0 Journal Article %1 Cher_2004_C797 %A Chernysh, Olga %A Condrescu, Madalina %A Reeves, John P %D 2004 %J Am. J. Physiol. Cell Physiol. %K 15151903 Allosteric Animals, CHO Calcium, Cells, Channels, Cytoplasm, Fura-2, Gov't, Hamsters, Humans, Muscle Mutation, Myocardium, Non-U.S. P.H.S., Proteins, Regulation, Research Sodium Support, Transfection, U.S. %N 3 %P C797--C806 %R 10.1152/ajpcell.00176.2004 %T Calcium-dependent regulation of calcium efflux by the cardiac sodium/calcium exchanger. %U http://dx.doi.org/10.1152/ajpcell.00176.2004 %V 287 %X Allosteric regulation by cytosolic Ca$^2+$ of Na$^+$/Ca$^2+$ exchange activity in the Ca$^2+$ efflux mode has received little attention because it has been technically difficult to distinguish between the roles of Ca$^2+$ as allosteric activator and transport substrate. In this study, we used transfected Chinese hamster ovary cells to compare the Ca$^2+$ efflux activities in nontransfected cells and in cells expressing either the wild-type exchanger or a mutant, Delta(241-680), that operates constitutively; i.e., its activity does not require allosteric Ca$^2+$ activation. Expression of the wild-type exchanger did not significantly lower the cytosolic Ca$^2+$ concentration (Ca$^2+$(i)) compared with nontransfected cells. During Ca$^2+$ entry through store-operated Ca$^2+$ channels, Ca$^2+$ efflux by the wild-type exchanger became evident only after Ca$^2+$(i) approached 100-200 nM. A subsequent decline in Ca$^2+$(i) was observed, suggesting that the activation process was time dependent. In contrast, Ca$^2+$ efflux activity was evident under all experimental conditions in cells expressing the constitutive exchanger mutant. After transient exposure to elevated Ca$^2+$(i), the wild-type exchanger behaved similarly to the constitutive mutant for tens of seconds after Ca$^2+$(i) had returned to resting levels. We conclude that Ca$^2+$ efflux activity by the wild-type exchanger is allosterically activated by Ca$^2+$, perhaps in a time-dependent manner, and that the activated state is briefly retained after the return of Ca$^2+$(i) to resting levels.

@article{Cher_2004_C797, abstract = {Allosteric regulation by cytosolic {C}a$^{2+}$ of {N}a$^{+}$/{C}a$^{2+}$ exchange activity in the {C}a$^{2+}$ efflux mode has received little attention because it has been technically difficult to distinguish between the roles of {C}a$^{2+}$ as allosteric activator and transport substrate. In this study, we used transfected Chinese hamster ovary cells to compare the {C}a$^{2+}$ efflux activities in nontransfected cells and in cells expressing either the wild-type exchanger or a mutant, Delta(241-680), that operates constitutively; i.e., its activity does not require allosteric {C}a$^{2+}$ activation. Expression of the wild-type exchanger did not significantly lower the cytosolic {C}a$^{2+}$ concentration ([{C}a$^{2+}$](i)) compared with nontransfected cells. During {C}a$^{2+}$ entry through store-operated {C}a$^{2+}$ channels, {C}a$^{2+}$ efflux by the wild-type exchanger became evident only after [{C}a$^{2+}$](i) approached 100-200 nM. A subsequent decline in [{C}a$^{2+}$](i) was observed, suggesting that the activation process was time dependent. In contrast, {C}a$^{2+}$ efflux activity was evident under all experimental conditions in cells expressing the constitutive exchanger mutant. After transient exposure to elevated [{C}a$^{2+}$](i), the wild-type exchanger behaved similarly to the constitutive mutant for tens of seconds after [{C}a$^{2+}$](i) had returned to resting levels. We conclude that {C}a$^{2+}$ efflux activity by the wild-type exchanger is allosterically activated by {C}a$^{2+}$, perhaps in a time-dependent manner, and that the activated state is briefly retained after the return of [{C}a$^{2+}$](i) to resting levels.}, added-at = {2009-06-03T11:20:58.000+0200}, author = {Chernysh, Olga and Condrescu, Madalina and Reeves, John P}, biburl = {https://www.bibsonomy.org/bibtex/28ef18afc89b7ed9c1ae9cf1680ebe2f4/hake}, description = {The whole bibliography file I use.}, doi = {10.1152/ajpcell.00176.2004}, file = {Cher_2004_C797.pdf:Cher_2004_C797.pdf:PDF}, interhash = {de81434a958d0f6fa4d69e0c7f29c811}, intrahash = {8ef18afc89b7ed9c1ae9cf1680ebe2f4}, journal = {Am. J. Physiol. Cell Physiol.}, keywords = {15151903 Allosteric Animals, CHO Calcium, Cells, Channels, Cytoplasm, Fura-2, Gov't, Hamsters, Humans, Muscle Mutation, Myocardium, Non-U.S. P.H.S., Proteins, Regulation, Research Sodium Support, Transfection, U.S.}, month = Sep, number = 3, pages = {C797--C806}, pii = {00176.2004}, pmid = {15151903}, timestamp = {2009-06-03T11:21:08.000+0200}, title = {Calcium-dependent regulation of calcium efflux by the cardiac sodium/calcium exchanger.}, url = {http://dx.doi.org/10.1152/ajpcell.00176.2004}, volume = 287, year = 2004 }