Calcium-activated and voltage-gated potassium channels of the pancreatic islet impart distinct and complementary roles during secretagogue induced electrical responses

Abstract

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. −/− 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.

Concerted Trafficking Regulation of Kv2.1 and KATP Channels by Leptin in Pancreatic β-Cells

“…Note we chose TEA rather than stromatoxin-1 because TEA inhibits Kv2.1 currents more completely. Although other K ϩ channels, including BK (large conductance calcium-and voltage-activated potassium channels), SK (small conductance calcium-activated potassium channels), K ATP , and other minor Kv channels, are also blocked by TEA to various extents, these channels are either a very small component of the overall K ϩ conductance under the recording condition (such as K ATP channels; data not shown) or they have been shown in previous studies to not have a significant role in determining the repolarization duration of action potentials in ␤-cells (31)(32)(33). TEA led to broadening of the action potential (Fig.…”

The voltage-dependent potassium channel subunit Kv2.1 regulates insulin secretion from rodent and human islets independently of its electrical function

“…Among likely contributors, the Kv2.1 isoform has been found to mediate the majority of Kv currents in rodent beta cells [2,4,33], although one or more other channels also contribute [34]. Inhibition or knockout of Kv2.1 enhances the electrical, intracellular Ca 2+ and secretory responses of rodent islets [1,2,4].…”

Electrophysiology of Islet Cells

“…SK3 protein has also been detected in human islets (Jacobson et al 2010). Up to now there is no investigation characterizing single-channel currents of SK1-SK3 in β cells, but it has been shown that SK1-SK3 channel inhibitors influence membrane potential and Ca 2+ oscillations (Tamarina et al 2003;Zhang et al 2005).…”