Calcium channels and the release of large dense core vesicles from neuroendocrine cells: spatial organization and functional coupling

The release of large dense core vesicles (LDCV) by neuroendocrine cells dis plays a very similar calcium dependence as found in synapses, yet, the orga nization of channels and vesicles is quite different. Various biophysical p roperties of the release process, notably a large delay (> 10 ms) between e xcitation and release and a high impact of mobile calcium buffers, suggest that, generally, vesicles and channels do not co-localize as in synapses, b ut are separated by a distance of 100-300 nm. This review focuses on the co nsequences of this organization for the functional coupling of calcium chan nels to LDCV-release in neuroendocrine cells. The large distance between LD CV and calcium channels in neuroendocrine cells obviates molecular interact ions between channels and fusion peptides and implies that each type of cal cium channel may be involved in release. Thus, preferential functional coup ling of specific calcium channel types to the exocytotic process may be com pletely lacking, as in melanotropes. Alternatively, it may be present to so me extent to induce differences in coupling efficacy between channel types, as in calf chromaffin cells and mouse pancreatic p-cells. Physiological me chanisms, like recruitment of channels through facilitation processes or su ppression of channels through inactivation, may change coupling characteris tics during activity. Due to the large distance between channels and vesicl es, single action potentials (APs) are usually insufficient to elicit relea se, and the coupling between individual APs and release is loose. Most neur oendocrine cells are therefore seen to fire in bursts, like pancreatic p-ce lls. Furthermore, a large variation in shape and duration of the APs, with APs of up to 300 ms as in melanotropes. acts as another mechanism to enhanc e stimulus secretion coupling. (C) 2000 Elsevier Science Ltd. All rights re served.