Co-localization of L-type Ca super(2+) channels and insulin-containing secretory granules and its significance for the initiation of exocytosis in mouse pancreatic B-cells

We have monitored L-type Ca super(2+) channel activity, local cytoplasmic Ca super(2+) transients, the distribution of insulin-containing secretory granules and exocytosis in individual mouse pancreatic B-cells. Subsequent to the opening of the Ca super(2+) channels, exocytosis is initiated with a latency < 100 ms. The entry of Ca super(2+) that precedes exocytosis is unevenly distributed over the cell and is concentrated to the region with the highest density of secretory granules. In this region, the cytoplasmic Ca super(2+) concentration is 5- to 10-fold higher than in the remainder of the cell reaching concentrations of several micromolar. Single-channel recordings confirm that the L-type Ca super(2+) channels are clustered in the part of the cell containing the secretory granules. This arrangement, which is obviously reminiscent of the "active zones" in nerve terminals, can be envisaged as being favourable to the B-cell as it ensures that the Ca super(2+) transient is maximal and restricted to the part of the cell where it is required to rapidly initiate exocytosis whilst at the same time minimizing the expenditure of metabolic energy to subsequently restore the resting Ca super(2+) concentration.