The whole‐cell Ca2+ release‐activated Ca2+ current, ICRAC, is regulated by the mitochondrial Ca2+ uniporter channel and is independent of extracellular and cytosolic Na+
Ca2+ entry through store‐operated Ca2+ release‐activated Ca2+ (CRAC) channels plays a central role in activation of a range of cellular responses over broad spatial and temporal bandwidths. Mitochondria, through their ability to take up cytosolic Ca2+, are important regulators of CRAC channel activi...
| Main Authors: | , , , |
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| Format: | Journal article |
| Language: | English |
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Wiley
2019
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| _version_ | 1797061674113433600 |
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| author | Samanta, K Bakowski, D Amin, N Parekh, A |
| author_facet | Samanta, K Bakowski, D Amin, N Parekh, A |
| author_sort | Samanta, K |
| collection | OXFORD |
| description | Ca2+ entry through store‐operated Ca2+ release‐activated Ca2+ (CRAC) channels plays a central role in activation of a range of cellular responses over broad spatial and temporal bandwidths. Mitochondria, through their ability to take up cytosolic Ca2+, are important regulators of CRAC channel activity under physiological conditions of weak intracellular Ca2+ buffering. The mitochondrial Ca2+ transporter(s) that regulates CRAC channels is unclear and could involve the 40 kDa mitochondrial Ca2+ uniporter (MCU) channel or the Na+–Ca2+–Li+ exchanger (NCLX). Here, we have investigated the involvement of these mitochondrial Ca2+ transporters in supporting the CRAC current (ICRAC) under a range of conditions in RBL mast cells. Knockdown of the MCU channel impaired the activation of ICRAC under physiological conditions of weak intracellular Ca2+ buffering. In strong Ca2+ buffer, knockdown of the MCU channel did not inhibit ICRAC development demonstrating that mitochondria regulate CRAC channels under physiological conditions by buffering of cytosolic Ca2+ via the MCU channel. Surprisingly, manipulations that altered extracellular Na+, cytosolic Na+ or both failed to inhibit the development of ICRAC in either strong or weak intracellular Ca2+ buffer. Knockdown of NCLX also did not affect ICRAC. Prolonged removal of external Na+ also had no significant effect on store‐operated Ca2+ entry, on cytosolic Ca2+ oscillations generated by receptor stimulation or on CRAC channel‐driven gene expression. In the RBL mast cell, Ca2+ flux through the MCU but not NCLX is indispensable for activation of ICRAC. |
| first_indexed | 2024-03-06T20:34:37Z |
| format | Journal article |
| id | oxford-uuid:3231e726-e838-4b96-bbb7-cf66492deeca |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T20:34:37Z |
| publishDate | 2019 |
| publisher | Wiley |
| record_format | dspace |
| spelling | oxford-uuid:3231e726-e838-4b96-bbb7-cf66492deeca2022-03-26T13:12:38ZThe whole‐cell Ca2+ release‐activated Ca2+ current, ICRAC, is regulated by the mitochondrial Ca2+ uniporter channel and is independent of extracellular and cytosolic Na+Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:3231e726-e838-4b96-bbb7-cf66492deecaEnglishSymplectic Elements at OxfordWiley2019Samanta, KBakowski, DAmin, NParekh, ACa2+ entry through store‐operated Ca2+ release‐activated Ca2+ (CRAC) channels plays a central role in activation of a range of cellular responses over broad spatial and temporal bandwidths. Mitochondria, through their ability to take up cytosolic Ca2+, are important regulators of CRAC channel activity under physiological conditions of weak intracellular Ca2+ buffering. The mitochondrial Ca2+ transporter(s) that regulates CRAC channels is unclear and could involve the 40 kDa mitochondrial Ca2+ uniporter (MCU) channel or the Na+–Ca2+–Li+ exchanger (NCLX). Here, we have investigated the involvement of these mitochondrial Ca2+ transporters in supporting the CRAC current (ICRAC) under a range of conditions in RBL mast cells. Knockdown of the MCU channel impaired the activation of ICRAC under physiological conditions of weak intracellular Ca2+ buffering. In strong Ca2+ buffer, knockdown of the MCU channel did not inhibit ICRAC development demonstrating that mitochondria regulate CRAC channels under physiological conditions by buffering of cytosolic Ca2+ via the MCU channel. Surprisingly, manipulations that altered extracellular Na+, cytosolic Na+ or both failed to inhibit the development of ICRAC in either strong or weak intracellular Ca2+ buffer. Knockdown of NCLX also did not affect ICRAC. Prolonged removal of external Na+ also had no significant effect on store‐operated Ca2+ entry, on cytosolic Ca2+ oscillations generated by receptor stimulation or on CRAC channel‐driven gene expression. In the RBL mast cell, Ca2+ flux through the MCU but not NCLX is indispensable for activation of ICRAC. |
| spellingShingle | Samanta, K Bakowski, D Amin, N Parekh, A The whole‐cell Ca2+ release‐activated Ca2+ current, ICRAC, is regulated by the mitochondrial Ca2+ uniporter channel and is independent of extracellular and cytosolic Na+ |
| title | The whole‐cell Ca2+ release‐activated Ca2+ current, ICRAC, is regulated by the mitochondrial Ca2+ uniporter channel and is independent of extracellular and cytosolic Na+ |
| title_full | The whole‐cell Ca2+ release‐activated Ca2+ current, ICRAC, is regulated by the mitochondrial Ca2+ uniporter channel and is independent of extracellular and cytosolic Na+ |
| title_fullStr | The whole‐cell Ca2+ release‐activated Ca2+ current, ICRAC, is regulated by the mitochondrial Ca2+ uniporter channel and is independent of extracellular and cytosolic Na+ |
| title_full_unstemmed | The whole‐cell Ca2+ release‐activated Ca2+ current, ICRAC, is regulated by the mitochondrial Ca2+ uniporter channel and is independent of extracellular and cytosolic Na+ |
| title_short | The whole‐cell Ca2+ release‐activated Ca2+ current, ICRAC, is regulated by the mitochondrial Ca2+ uniporter channel and is independent of extracellular and cytosolic Na+ |
| title_sort | whole cell ca2 release activated ca2 current icrac is regulated by the mitochondrial ca2 uniporter channel and is independent of extracellular and cytosolic na |
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