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Research Papers
Store-Operated Orai1 and IP3 Receptor-Operated TRPC1 Channel:
Separation of the Siamese Twins
Vladislav V. Zarayskiy, Francisco Monje, Krisztina Peter, Peter Csutora, Boris Khodorov and Victoria M. Bolotina
volume 1 | issue 4
July/AugustPages: 246 - 252
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Store-operated channels (SOC) are known to be physiologically activated following agonist-induced IP3 production and depletion of Ca2+ stores. Here we present molecular, biophysical and mechanistic evidence that two ubiquitously expressed plasma membrane channels may be responsible for creating a complex and sometimes controversial SOC image: one being a real SOC encoded by Orai1 and activated exclusively upon depletion of Ca2+ stores (via iPLA2β -dependent pathway), while the second one is an IP3 receptor-operated channel (IP3ROC) encoded by TRPC1 and activated via its conformational coupling with IP3 receptor. In RBL-2H3 cells endogenously expressing Orai1 and TRPC1, we unmasked and characterized whole-cell current through IP3ROC channels that was hiding behind some familiar fingerprints of ICRAC, a current through the classical Ca2+-selective SOC (CRAC) channels. We discriminated these currents by their molecular identity, selectivity and different requirements for store depletion, IP3, iPLA2β and conformational coupling to IP3 receptor. New knowledge on the properties and co-existence of Orai1-encoded SOC and TRPC1-encoded IP3ROC, and the use of experimental approaches introduced in this manuscript should help avoid further confusion about these channels, and open new exciting possibilities for their independent studies.
Authors
Vladislav V. Zarayskiy
Boston University School of Medicine
Francisco Monje
Boston University School of Medicine
Krisztina Peter
Boston University School of Medicine
Peter Csutora
Boston University School of Medicine
Boris Khodorov
Institure of General Pathology, Moscow
Victoria M. Bolotina
Boston Universtity School of Medicine
We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link:
Download PDF If the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.