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Calcium‐activated and voltage‐gated potassium channels of the pancreatic islet impart distinct and complementary roles during secretagogue induced electrical responses
Author(s) -
Jacobson David A.,
Mendez Felipe,
Thompson Michael,
Torres Jacqueline,
Cochet Olivia,
Philipson Louis H.
Publication year - 2010
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.2010.190207
Subject(s) - apamin , potassium channel , repolarization , endocrinology , sk channel , secretagogue , bk channel , medicine , chemistry , islet , potassium channel blocker , inward rectifier potassium ion channel , calcium activated potassium channel , voltage dependent calcium channel , charybdotoxin , calcium , biology , electrophysiology , ion channel , insulin , biochemistry , receptor
Glucose‐induced β‐cell action potential (AP) repolarization is regulated by potassium efflux through voltage gated (Kv) and calcium activated (K Ca ) potassium channels. Thus, ablation of the primary Kv channel of the β‐cell, Kv2.1, causes increased AP duration. However, Kv2.1 −/− islet electrical activity still remains sensitive to the potassium channel inhibitor tetraethylammonium. Therefore, we utilized Kv2.1 −/− islets to characterize Kv and K Ca channels and their respective roles in modulating the β‐cell AP. The remaining Kv current present in Kv2.1 −/− β‐cells is inhibited with 5 μm CP 339818. Inhibition of the remaining Kv current in Kv2.1 −/− mouse β‐cells increased AP firing frequency by 39.6% but did not significantly enhance glucose stimulated insulin secretion (GSIS). The modest regulation of islet AP frequency by CP 339818 implicates other K + channels, possibly K Ca channels, in regulating AP repolarization. Blockade of the K Ca channel BK with slotoxin increased β‐cell AP amplitude by 28.2%, whereas activation of BK channels with isopimaric acid decreased β‐cell AP amplitude by 30.6%. Interestingly, the K Ca channel SK significantly contributes to Kv2.1 −/− mouse islet AP repolarization. Inhibition of SK channels decreased AP firing frequency by 66% and increased AP duration by 67% only when Kv2.1 is ablated or inhibited and enhanced GSIS by 2.7‐fold. Human islets also express SK3 channels and their β‐cell AP frequency is significantly accelerated by 4.8‐fold with apamin. These results uncover important repolarizing roles for both Kv and K Ca channels and identify distinct roles for SK channel activity in regulating calcium‐ versus sodium‐dependent AP firing.