Pancreatic K3.1 channels in health and disease.

Ion channels play an important role for regulation of the exocrine and the endocrine pancreas. This review focuses on the Ca-regulated K channel K3.1, encoded by the gene, which is present in both parts of the pancreas. In the islets of Langerhans, K3.1 channels are involved in the regulation of membrane potential oscillations characterizing nutrient-stimulated islet activity. Channel upregulation is induced by gluco- or lipotoxic conditions and might contribute to micro-inflammation and impaired insulin release in type 2 diabetes mellitus as well as to diabetes-associated renal and vascular complications. In the exocrine pancreas K3.1 channels are expressed in acinar and ductal cells. They are thought to play a role for anion secretion during digestion but their physiological role has not been fully elucidated yet. Pancreatic carcinoma, especially pancreatic ductal adenocarcinoma (PDAC), is associated with drastic overexpression of K3.1. For pharmacological targeting of K3.1 channels, we are discussing the possible benefits K3.1 channel inhibitors might provide in the context of diabetes mellitus and pancreatic cancer, respectively. We are also giving a perspective for the use of a fluorescently labeled derivative of the K3.1 blocker senicapoc as a tool to monitor channel distribution in pancreatic tissue. In summary, modulating K3.1 channel activity is a useful strategy for exo-and endocrine pancreatic disease but further studies are needed to evaluate its clinical suitability.