CaM kinase II-dependent mobilization of secretory granules underlies acetylcholine-induced stimulation of exocytosis in mouse pancreatic B-cells.

Journal article

1. Measurements of cell capacitance were used to investigate the mechanisms by which acetylcholine (ACh) stimulates Ca2+-induced exocytosis in single insulin-secreting mouse pancreatic B-cells. 2. ACh (250 microM) increased exocytotic responses elicited by voltage-clamp depolarizations 2.3-fold. This effect was mediated by activation of muscarinic receptors and dependent on elevation of the cytoplasmic Ca2+ concentration ([Ca2+]i) attributable to mobilization of Ca2+ from intracellular stores. The latter action involved interference with the buffering of [Ca2+]i and the time constant (tau) for the recovery of [Ca2+]i following a voltage-clamp depolarization increased 5-fold. As a result, Ca2+ was present at concentrations sufficient to promote the replenishment of the readily releasable pool of granules (RRP; > 0.2 microM) for much longer periods in the presence than in the absence of the agonist. 3. The effect of Ca2+ on exocytosis was mediated by activation of CaM kinase II, but not protein kinase C, and involved both an increased size of the RRP from 40 to 140 granules and a decrease in tau for the refilling of the RRP from 31 to 19 s. 4. Collectively, the effects of ACh on the RRP and tau result in a > 10-fold stimulation of the rate at which granules are supplied for release.

Authors: Gromada, J; Høy, M; Renström, E; Bokvist, K; Eliasson, L

• Publication status: Published
• Journal: Journal of physiology
• Volume: 518 ( Pt 3)
• Issue: 3
• Pages: 745-759
• Publication date: 1999-08-01
• DOI: 10.1111/j.1469-7793.1999.0745p.x
• EISSN: 1469-7793
• ISSN: 0022-3751
• Language: English
• Keywords: Exocytosis; Acetylcholine; Stimulation, Chemical; Calcium; Electrophysiology; Protein Kinase C; Cytoplasmic Granules; Animals; Calcium-Calmodulin-Dependent Protein Kinase Type 2; Muscarinic Agonists; Mice; Membrane Potentials; Calcium-Calmodulin-Dependent Protein Kinases; Electric Conductivity; Enzyme Inhibitors; Islets of Langerhans; Patch-Clamp Techniques; Kinetics