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This Article Full Text Full Text (PDF) All Versions of this Article: 546/1/175    most recent 2002.029959v2 2002.029959v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Kang, G. Articles by Holz, G. G. Search for Related Content PubMed PubMed Citation Articles by Kang, G. Articles by Holz, G. G.

Amplification of exocytosis by Ca²⁺-induced Ca²⁺ release in INS-1 pancreatic cells

Guoxin Kang and George G. Holz

Functional coupling between Ca²⁺-induced Ca²⁺ release (CICR) and quantal exocytosis in 5-hydroxytryptamine-loaded INS-1 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 [Ca²⁺]_i. The action of Ex-4 was reproduced by treatment with caffeine, and the source of Ca²⁺ serving as a stimulus for exocytosis originated from ryanodine and thapsigargin-sensitive Ca²⁺ 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 Ca²⁺ concentration ([Ca²⁺]_B) was low (75-150 nM), whereas S-type exocytosis predominated under conditions in which the [Ca²⁺]_B was elevated (200-275 nM). Depolarization-induced Ca²⁺ influx triggered NS-type exocytosis in most cells tested, irrespective of [Ca²⁺]_B. It is concluded that CICR is a highly effective stimulus for exocytosis in INS-1 cells. The increase of [Ca²⁺]_i that accompanies CICR stimulates the asynchronous release of a small number of secretory granules under conditions of low [Ca²⁺]_B. When [Ca²⁺]_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 Ca²⁺-dependent exocytosis.