Ionic mechanisms in pancreatic β cell signaling |
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Authors: | Shao-Nian Yang Yue Shi Guang Yang Yuxin Li Jia Yu Per-Olof Berggren |
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Institution: | 1. The Rolf Luft Research Center for Diabetes and Endocrinology, Karolinska Institutet, SE-171 76, Stockholm, Sweden 3. National Engineering Laboratory for Druggable Gene and Protein Screening, Northeast Normal University, Changchun, 130024, China 2. Jilin Academy of Traditional Chinese Medicine, Changchun, 130021, China
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Abstract: | The function and survival of pancreatic β cells critically rely on complex electrical signaling systems composed of a series of ionic events, namely fluxes of K+, Na+, Ca2+ and Cl? across the β cell membranes. These electrical signaling systems not only sense events occurring in the extracellular space and intracellular milieu of pancreatic islet cells, but also control different β cell activities, most notably glucose-stimulated insulin secretion. Three major ion fluxes including K+ efflux through ATP-sensitive K+ (KATP) channels, the voltage-gated Ca2+ (CaV) channel-mediated Ca2+ influx and K+ efflux through voltage-gated K+ (KV) channels operate in the β cell. These ion fluxes set the resting membrane potential and the shape, rate and pattern of firing of action potentials under different metabolic conditions. The KATP channel-mediated K+ efflux determines the resting membrane potential and keeps the excitability of the β cell at low levels. Ca2+ influx through CaV1 channels, a major type of β cell CaV channels, causes the upstroke or depolarization phase of the action potential and regulates a wide range of β cell functions including the most elementary β cell function, insulin secretion. K+ efflux mediated by KV2.1 delayed rectifier K+ channels, a predominant form of β cell KV channels, brings about the downstroke or repolarization phase of the action potential, which acts as a brake for insulin secretion owing to shutting down the CaV channel-mediated Ca2+ entry. These three ion channel-mediated ion fluxes are the most important ionic events in β cell signaling. This review concisely discusses various ionic mechanisms in β cell signaling and highlights KATP channel-, CaV1 channel- and KV2.1 channel-mediated ion fluxes. |
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