Localized Ca2+ signals and highly coupled exocytosis in chromaffin cells

FERNANDO D. MARENGO

New Research on Signal Transduction

Nova Publishers

Año: 2006;

In neuroendocrine cells, such as adrenal chromaffin cells, the trigger for exocytosis is a localized Ca2+ increase near the cell membrane that develops after the activation of voltage-dependent Ca2+ channels. A combination of experimental data and theoretical analysis suggest that in response to membrane depolarization a narrow Ca2+ gradient of less than 1 mm from the cell membrane develops in the periphery of chromaffin cells in few milliseconds. This gradient is supposed to be responsible for the activation of ready releasable vesicles exocytosis. Is this Ca2+ gradient homogeneously distributed around the cell membrane? Ca2+ imaging of chromaffin cells gives no clear answers to this question. The generation of peripheral hotspots in response to single short depolarizations has been observed in bovine chromaffin cells, but fairly continuous radial gradients were also reported. Ca2+ entry through channels is spatially discontinuous in nature, but the resultant discontinuity in Ca2+ signal could be below regular light microscopy resolution. Some authors addressed that problem, and using evanescent field imaging of near membrane [Ca2+], they were able to measure single Ca2+ microdomains associated to the activation of voltage gated Ca2+ influx. One possible consequence of such uneven distribution of Ca2+ signal is that ready releasable vesicles could be randomly distributed at variable distances respect to the Ca2+ sources. This scenario will provoke that certain vesicles would be coupled more efficiently to Ca2+ signal than others. This reasonable hypothesis was proposed as one explanation for the experimentally observed exocytosis of a small group of vesicles, specifically coupled to short pulse depolarizations, i.e. the immediately releasable pool (IRP). This chapter summarizes and analyzes the available information respect to localized Ca2+ signals provoked by channel activation in neuroendocrine cells, and their coupling with the exocytotic machinery. In a second part, highly coupled vesicle pools, their characteristics and possible regulation mechanisms are examined