The Role of Potassium and Calcium Ion Channels in Membrane Potential Regulation and Diabetes Mellitus

Abstract

Potassium (K+) and calcium (Ca2+) ion channels are important regulators of cell electrical activity, membrane potential, intracellular calcium homeostasis, hormone production, vascular tone, neuronal excitability and metabolic function. Their coordinated activity is especially crucial in pancreatic β-cells, where variations in membrane potential act as the electrical coupling between glucose metabolism and insulin release. In healthy β-cells, glucose metabolism increases the intracellular ATP/ADP ratio, closes ATP-sensitive potassium (KATP) channels, depolarises the membrane, activates voltage-dependent calcium channels and increases cytosolic Ca2+, which induces insulin granule exocytosis. Potassium channels of several types, including voltage-dependent potassium channels and calcium-activated potassium channels, then regulate the pattern of electrical activity and membrane repolarisation. Thus, calcium channels not only constitute sources of intracellular Ca2+ but also play an essential part in the stimulus secretion coupling mechanism. In diabetes mellitus altered expression, activity and control of potassium and calcium channels can affect membrane potential, calcium homeostasis and insulin production. Hyperglycaemia, lipotoxicity, oxidative stress, mitochondrial dysfunction, inflammation and advanced glycation can alter ion-channel function and lead to β-cell failure. Similar channel anomalies are seen in vascular smooth muscle, endothelial cells, neurones and erythrocytes, possibly contributing to vascular dysfunction, diabetic neuropathy and other consequences. The knowledge on the interplay between potassium and calcium channels provides an important basis to explain the cellular mechanisms of diabetes mellitus and may help to create channel-targeted treatments.