CRAC channel activity pulsates during cytosolic Ca2+ oscillations
Year: 2025
Type: article
Abstract: Intracellular Ca 2+ ions are used as second messengers throughout the phylogenetic tree. They are indispensable for diverse biological processes ranging from fertilization to cell death. In Metazoans, signaling information is conveyed via the amplitude, frequency, and spatial profile of cytosolic Ca 2+ oscillations. In non-excitable cells, these oscillations generally arise from regenerative release of Ca 2+ from inositol 1,4,5-trisphosphate (InsP 3 )-sensitive intracellular stores, which are refilled by entry of Ca 2+ through Ca 2+ release-activated Ca 2+ (CRAC) channels in the plasma membrane. However, the precise contribution of these store-operated CRAC channels to Ca 2+ oscillations has remained controversial for decades. One view proposes that CRAC channels remain open throughout stimulation, functioning as the pacemaker in setting Ca 2+ oscillation frequency. An alternative hypothesis is that channel activity oscillates in parallel with InsP 3 -driven regenerative Ca 2+ release. Here, by tethering a genetically encoded Ca 2+ indicator to the pore-forming subunit of the CRAC channel, Orai1, we distinguish between these hypotheses and demonstrate that CRAC channel activity fluctuates in phase with cytosolic Ca 2+ oscillations during physiological levels of stimulation. We also find that spatially distinct CRAC channel clusters fire in a coordinated manner, revealing that CRAC channels are not independent units but might function in a synchronized manner to provide pulses of Ca 2+ signal at the same time.
Source: Journal of Biological Chemistry
Language: English
Topic: Ion Channels and Receptors
Subfield: Sensory Systems
Field: Neuroscience
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,430
OpenAlex ID: W4409726825