Abstract

This editorial refers to ‘Emergence of Orai3 activity during cardiac hypertrophy’ by Y. Saliba et al. , doi:10.1093/cvr/cvu207 .

Our understanding of cardiomyocyte Ca2+ handling is primarily based on the regulation of voltage-gated Ca2+ entry, via L-type Ca2+ channels (LTCCs), and the resulting Ca2+-induced Ca2+ release from the sarcoplasmic reticulum (SR) required for excitation–contraction coupling. Ca2+ is widely recognized as playing a key signalling role in all cells, and in cardiomyocytes the most commonly accepted pathway involves Ca2+ release from intracellular stores such as the endoplasmic reticulum (ER)/SR and the nuclear envelope. However, in non-excitable cells, agonist-mediated increases in intracellular Ca2+ are known to occur as a result of Ca2+ entry across the plasma membrane. The most widely studied of these pathways is store-operated Ca2+ entry (SOCE) as described by Putney1 where Inositol 1, 4, 5 Triphosphate (IP3)-induced release of Ca2+ from ER/SR stores triggered a subsequent influx of extracellular Ca2+, which was required both for subsequent activation of downstream signalling pathways and also for refilling of ER/SR. Such Ca2+ signals have been shown to play a key role in the regulation of diverse cellular responses, including metabolism, transcription, and differentiation. One of the earliest reports demonstrating that SOCE contributed to Ca2+ signalling in cardiomyocytes was in 2002 where Marchase and colleagues2 showed that activation of nuclear factor of activated T-cells …