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(Circulation Research. 2009;104:e56.)
© 2009 American Heart Association, Inc.

Letter to the Editor

STIM1/Orai1, I_CRAC, and Endothelial SOC

Mohamed Trebak

Center for Cardiovascular Sciences, Albany Medical College, Albany, NY, E-mail trebakm@mail.amc.edu

An extract of the first 250 words of the full text is provided, because this article has no abstract.

To the Editor:

Store-operated calcium (Ca²⁺) entry (SOCE) is an evolutionarily conserved pathway of regulated Ca²⁺ entry into cells whereby the depletion of Ca²⁺ from internal stores signals the activation of plasma membrane SOC channels.^1,2 Nonselective canonical transient receptor potential channel (TRPC) proteins were investigated as potential components of SOC channels in mammals. However, the resulting literature offer no consensus among investigators, and the role of TRPCs in encoding SOC remains a contentious issue.² In our recent study,³ we challenged the role of TRPCs in endothelial cell (EC) SOCE by showing evidence for I_CRAC in ECs encoded by STIM1 and Orai1 independently of TRPC1 and TRPC4. In a letter to Circulation Research,⁴ Beech pointed out the discrepancies between previously published data and ours and contended: (1) "that although the biophysical properties of the I_CRAC recorded in divalent-free (DVF) solutions are convincing, its small size in the presence of extracellular Ca²⁺ and intracellular BAPTA makes its existence uncertain and that observation of current with BAPTA in the pipette is not proof that it is store-operated"; and (2) we "failed to provide confidence for the knockdown of TRPC1." We reject these contentions and maintain that I_CRAC encoded by STIM1/Orai1 accounts for EC SOCE based on the following evidence:

First, it has been clearly established that I_CRAC can be activated to the same extent with any means that deplete the stores; these include: BAPTA or inositol-1,4,5-trisphosphate (IP₃) dialysis through the pipette; SERCA inhibitors or ionomycin applied . . . [Full Text of this Article]