Physiological significance of SK4 channels in pancreatic β-cell oscillations

Pancreatic beta-cells show oscillations in membrane potential (Vm), the cytosolic Ca (2+) concentration ([Ca (2+) ]c) and finally insulin secretion. It is well accepted that the initiation of a burst phase with action potentials is mediated by voltage-dependent Ca (2+) (and Na (+) ) channels. The mechanism triggering the onset of interburst phases is less clear. The exact nature of the K (+) channels that hyperpolarize Vm to maintain the rhythmic activity is unknown. In 1999 Göpel and co-workers (1) described a current termed Kslow and claimed that this current terminates the burst phases. KATP current is a part of the Kslow current. We could show that the Ca (2+) -dependent K (+) current through K (+) channels of intermediate conductance (SK4, KCa3.1 or IK1) also contributes to the Kslow current. We suggest that the Kslow current is composed of two currents through metabolism-regulated K (+) channels, KATP (regulated by ATP) and SK4 (regulated by Ca (2+) ). We further propose that the SK4 component of the Kslow current can trigger oscillations in mice without functioning KATP channels.