Calcium signaling in non-excitable cells: Ca2+ release and influx are independent events linked to two plasma membrane Ca2+ entry channels
✍ Scribed by Ranjana Chakrabarti; Rabindranath Chakrabarti
- Publisher
- John Wiley and Sons
- Year
- 2006
- Tongue
- English
- Weight
- 206 KB
- Volume
- 99
- Category
- Article
- ISSN
- 0730-2312
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✦ Synopsis
The regulatory mechanism of Ca 2þ influx into the cytosol from the extracellular space in non-excitable cells is not clear. The ''capacitative calcium entry'' (CCE) hypothesis suggested that Ca 2þ influx is triggered by the IP 3mediated emptying of the intracellular Ca 2þ 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 2þ release does not affect Ca 2þ influx, and the experimental protocols used to demonstrate CCE can stimulate Ca 2þ influx by means other than emptying of the Ca 2þ stores. In addition, we have presented the reports showing that IP 3mediated Ca 2þ release is linked to a Ca 2þ entry from the extracellular space, which does not increase cytosolic [Ca 2þ ] prior to Ca 2þ release. Based on these and other reports, we have provided a model of Ca 2þ signaling in non-excitable cells, in which IP 3 -mediated emptying of the intracellular Ca 2þ store triggers entry of Ca 2þ directly into the store, through a plasma membrane TRPC channel. Thus, emptying and direct refilling of the Ca 2þ stores are repeated in the presence of IP 3 , giving rise to the transient phase of oscillatory Ca 2þ release. Direct Ca 2þ entry into the store is regulated by its filling status in a negative and positive manner through a Ca 2þ -binding protein and Stim1/Orai complex, respectively. The sustained phase of Ca 2þ influx is triggered by diacylglycerol (DAG) through the activation of another TRPC channel, independent of Ca 2þ release. The plasma membrane IP 3 receptor (IP 3 R) plays an essential role in Ca 2þ influx, by interacting with the DAGactivated TRPC, without the requirement of binding to IP 3 .