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Amplification of exocytosis by Ca 2+ ‐induced Ca 2+ release in INS‐1 pancreatic β cells
Author(s) -
Kang Guoxin,
Holz George G.
Publication year - 2003
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2002.029959
Subject(s) - exocytosis , chemistry , biophysics , depolarization , endocrinology , medicine , secretion , biology , biochemistry
Functional coupling between Ca 2+ ‐induced Ca 2+ release (CICR) and quantal exocytosis in 5‐hydroxytryptamine‐loaded INS‐1 β cells was assessed through the use of carbon fibre amperometry in combination with Fura‐2. CICR was evoked by the glucagon‐like‐peptide‐1 (GLP‐1) receptor agonist exendin‐4 (Ex‐4) and was accompanied by quantal secretory events appearing as amperometric current spikes time‐locked to the increase of [Ca 2+ ] i . The action of Ex‐4 was reproduced by treatment with caffeine, and the source of Ca 2+ serving as a stimulus for exocytosis originated from ryanodine and thapsigargin‐sensitive Ca 2+ stores. Two distinct patterns of exocytosis occurred within 5 s following the initiation of CICR. Non‐summating exocytosis (NS‐type) was defined as multiple asynchronous current spikes, and the half‐height duration of each spike was 12‐48 ms. Summating exocytosis (S‐type) was defined as a cluster of spikes. It generated a macroscopic current, the half‐height duration of which was 243‐682 ms. The release charge of S‐type exocytosis was 3.2‐fold greater than that of NS‐type when measured 2 s following the initiation of secretion. NS‐type exocytosis was observed frequently under conditions in which the basal Ca 2+ concentration ([Ca 2+ ] B ) was low (75‐150 n m ), whereas S‐type exocytosis predominated under conditions in which the [Ca 2+ ] B was elevated (200‐275 n m ). Depolarization‐induced Ca 2+ influx triggered NS‐type exocytosis in most cells tested, irrespective of [Ca 2+ ] B . It is concluded that CICR is a highly effective stimulus for exocytosis in INS‐1 cells. The increase of [Ca 2+ ] i that accompanies CICR stimulates the asynchronous release of a small number of secretory granules under conditions of low [Ca 2+ ] B . When [Ca 2+ ] B is slightly elevated, CICR targets a much larger pool of secretory granules that undergo summating exocytosis. The transition from NS‐type to S‐type exocytosis may represent an amplification mechanism for Ca 2+ ‐dependent exocytosis.