Calcium influx into pancreatic α-cells through voltage-dependent calcium channels (VDCCs) is required for glucagon (GCG) secretion and the mechanisms that mediate this process become defective during the pathogenesis of diabetes. Potassium channels are key regulators of membrane potential (Vm), and thus, modulate VDCC activity. However, the role of calcium-activated potassium (KCa) channels in α-cell calcium handling and GCG secretion have not been determined.

The aim of this study was to investigate the importance of KCa channels to α-cell electrical excitability, calcium handling, and GCG secretion. α-cells display a KCa current, which is partially inhibited by blocking small conductance KCa (SK) or big conductance KCa (BK) channels. Inhibition of P/Q-type VDCCs, sarco/endoplasmic reticulum (ER) calcium-ATPases (SERCAs), and KATP channels also partially inhibit this current. It is likely that calcium influx through VDCCs triggers calcium-induced calcium release (CICR) from ER calcium stores activating α-cell KCa channels. The inhibition of SK channels transiently increases calcium influx into α-cells at 1 mM glucose; however, over time intracellular calcium decreases. This may be due to voltage-dependent inactivation of α-cell VDCCs. Interestingly, SK channel inhibition reduces GCG secretion at 1 mM glucose while SST secretion is unaffected. Thus, it is likely that this is an intrinsic α-cell effect. These findings demonstrate that α-cells possess a KCa current and that its activation is important for α-cell electrical activity, Ca2+ handling, and GCG secretion.


M. Dickerson: None. M.K. Altman: None. P. Dadi: None. N.C. Vierra: None. D. Jacobson: None.

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