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. 2004 Dec;124(6):623-5.
doi: 10.1085/jgp.200409206.

Insulin secretion: a high-affinity Ca2+ sensor after all?

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Insulin secretion: a high-affinity Ca2+ sensor after all?

Sebastian Barg et al. J Gen Physiol. 2004 Dec.
No abstract available

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Figures

F<sc>igure</sc> 1.
Figure 1.
(A and B) Schematic illustrating the presence of two populations of granules in β-cells with distinct Ca2+ sensitivities. Granules with a low-affinity Ca2+ sensor need to be associated with the voltage-gated Ca2+-channels, whereas those equipped with a high-affinity Ca2+ sensor (HCSP) undergo exocytosis in response to a global elevation of cytoplasmic Ca2+. A and B show the situation under basal conditions and following activation of PKA or PKC, respectively. In A, only granules close to the Ca2+ channels are exposed to sufficiently high Ca2+ concentrations to undergo exocytosis (gray areas). In B, moderate but global increases in cytoplasmic Ca2+ (dashed lines; both by Ca2+ influx through the plasma membrane Ca2+ channels and release from intracellular Ca2+ stores) suffice to trigger exocytosis of HCSP granules, which need not be associated with the Ca2+ channels. In addition to the Ca2+-dependent processes discussed here that are involved in the triggering of exocytosis, Ca2+-dependent steps have also been described for more upstream events such as priming/mobilization (indicated by arrow in B). (C) Exocytosis as a function of cytoplasmic Ca2+ concentration for the low-affinity (dashed line) and high-affinity (HCSP; gray line) processes and the sum of the two (i.e., HCSP plus RRP; black line). Note that HCSP attains it maximum already at Ca2+ concentrations <10 μM. Data are derived from Barg et al. (2001) assuming a depolarization lasting 50 ms (corresponding to the β-cell action potential) and Wan et al. (2004). The sum of the two predicts a gradual stimulation of exocytosis over a wide range of calcium concentrations (0.5–30 μM).

References

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