First Author | Jacobson DA | Year | 2010 |
Journal | J Physiol | Volume | 588 |
Issue | Pt 18 | Pages | 3525-37 |
PubMed ID | 20643768 | Mgi Jnum | J:177330 |
Mgi Id | MGI:5294744 | Doi | 10.1113/jphysiol.2010.190207 |
Citation | Jacobson DA, et al. (2010) Calcium-activated and voltage-gated potassium channels of the pancreatic islet impart distinct and complementary roles during secretagogue induced electrical responses. J Physiol 588(Pt 18):3525-37 |
abstractText | Glucose-induced beta-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 beta-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 beta-cell AP. The remaining Kv current present in Kv2.1(-/-) beta-cells is inhibited with 5 muM CP 339818. Inhibition of the remaining Kv current in Kv2.1(-/-) mouse beta-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 beta-cell AP amplitude by 28.2%, whereas activation of BK channels with isopimaric acid decreased beta-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 beta-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. |