Subcellular trafficking and endocytic recycling of K channels.

Sarcolemmal/plasmalemmal ATP-sensitive K (K) channels have key roles in many cell types and tissues. Hundreds of studies have described how the K channel activity and ATP sensitivity can be regulated by changes in the cellular metabolic state, by receptor signaling pathways and by pharmacological interventions. These alterations in channel activity directly translate to alterations in cell or tissue function, that can range from modulating secretory responses, such as insulin release from pancreatic β-cells or neurotransmitters from neurons, to modulating contractile behavior of smooth muscle or cardiac cells to elicit alterations in blood flow or cardiac contractility. It is increasingly becoming apparent, however, that K channels are regulated beyond changes in their activity. Recent studies have highlighted that K channel surface expression is a tightly regulated process with similar implications in health and disease. The surface expression of K channels is finely balanced by several trafficking steps including synthesis, assembly, anterograde trafficking, membrane anchoring, endocytosis, endocytic recycling, and degradation. This review aims to summarize the physiological and pathophysiological implications of K channel trafficking and mechanisms that regulate K channel trafficking. A better understanding of this topic has potential to identify new approaches to develop therapeutically useful drugs to treat K channel-related diseases.