Fast Ca(2+)-dependent inactivation of the store-operated Ca2+ current (ISOC) in liver cells: a role for calmodulin

The Journal of Physiology
T LitjensGrigori Y Rychkov

Abstract

Store-operated Ca2+ channels (SOCs) provide a major pathway for Ca2+ entry in non-excitable cells. SOCs in immortalized liver cells are highly selective for Ca2+ over other cations and are similar to well-studied Ca2+ release activated Ca2+ (CRAC) channels in haematopoietic cell lines. In the present work, employing H4IIE liver cells, we investigated fast inactivation of SOC current (ISOC), which occurs at membrane potentials below -60 mV. This inactivation was significantly reduced when BAPTA, a faster Ca2+ buffer, was used instead of EGTA, and was completely abolished if Na+ was used as a charge carrier in the absence of divalent cations in the external medium. These results suggested that fast inactivation of SOCs in H4IIE cells was Ca2+ dependent and was similar to the fast inactivation of CRAC channels. Experiments showing that the fast inactivation of ISOC was not affected by the disruption of actin by latrunculin B indicate that the cytoskeleton is unlikely to be involved. To elucidate the mechanism of Ca2+ dependence, a possible role of calmodulin (CaM) in SOCs' fast inactivation was investigated. The CaM inhibitors Mas-7 and calmidazolium failed to affect ISOC fast inactivation, whereas over-expression of a CaM inhibit...Continue Reading

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Citations

Aug 24, 2012·Nature Reviews. Molecular Cell Biology·Jonathan SoboloffDonald L Gill
Aug 27, 2009·Proceedings of the National Academy of Sciences of the United States of America·Franklin M MullinsRichard S Lewis
Jul 28, 2011·Cold Spring Harbor Perspectives in Biology·Richard S Lewis
Feb 7, 2009·Clinical and Experimental Pharmacology & Physiology·Greg J BarrittGrigori Y Rychkov
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Feb 27, 2014·Proceedings of the National Academy of Sciences of the United States of America·Ehsan KheradpezhouhGrigori Y Rychkov
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Jan 12, 2010·Archives of Biochemistry and Biophysics·Minh-Son ToGrigori Y Rychkov

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