Calcium signaling in non-excitable cells: Ca(2+) release and influx are independent events linked to two plasma membrane Ca(2+) entry channels.
The regulatory mechanism of Ca(2+) influx into the cytosol from the extracellular space in non-excitable cells is not clear. The "capacitative calcium entry" (CCE) hypothesis suggested that Ca(2+) influx is triggered by the IP(3)-mediated emptying of the intracellular Ca(2+) stores. However, there is no clear evidence for CCE and its mechanism remains elusive. In the present work, we have provided the reported evidences to show that inhibition of IP(3)-dependent Ca(2+) release does not affect Ca(2+) influx, and the experimental protocols used to demonstrate CCE can stimulate Ca(2+) influx by means other than emptying of the Ca(2+) stores. In addition, we have presented the reports showing that IP(3)-mediated Ca(2+) release is linked to a Ca(2+) entry from the extracellular space, which does not increase cytosolic [Ca(2+)] prior to Ca(2+) release. Based on these and other reports, we have provided a model of Ca(2+) signaling in non-excitable cells, in which IP(3)-mediated emptying of the intracellular Ca(2+) store triggers entry of Ca(2+) directly into the store, through a plasma membrane TRPC channel. Thus, emptying and direct refilling of the Ca(2+) stores are repeated in the presence of IP(3), giving rise to the transient phase of oscillatory Ca(2+) release. Direct Ca(2+) entry into the store is regulated by its filling status in a negative and positive manner through a Ca(2+)-binding protein and Stim1/Orai complex, respectively. The sustained phase of Ca(2+) influx is triggered by diacylglycerol (DAG) through the activation of another TRPC channel, independent of Ca(2+) release. The plasma membrane IP(3) receptor (IP(3)R) plays an essential role in Ca(2+) influx, by interacting with the DAG-activated TRPC, without the requirement of binding to IP(3). J. Cell. Biochem. 99: 1503-1516, 2006. (c) 2006 Wiley-Liss, Inc.[1]References
- Calcium signaling in non-excitable cells: Ca(2+) release and influx are independent events linked to two plasma membrane Ca(2+) entry channels. Chakrabarti, R., Chakrabarti, R. J. Cell. Biochem. (2006) [Pubmed]
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