Homeostatic Regulation of Neuronal Excitability by K+ Channels in Normal and Diseased Brains

Abstract

K+-selective ion channels are critical determinants of membrane excitability in neuronal cells. Like many other cells in our body, neuronal cells have a propensity to maintain their homeostasis. Action potential firing is the most important function to maintain in brain neurons, as they are the elements of neural networks. If one element fires action potentials at an abnormally high rate, the entire network could become epileptic. Therefore, brain neurons adjust their intrinsic membrane excitability to maintain the firing rate within their own optimal operational range. When a neuron receives an enormous input, it will reduce the membrane excitability to prevent overshooting. When it is deprived of stimulus, the membrane becomes more excitable to avoid total quiescence. The homeostatic regulation of intrinsic excitability provides stability to the neural network in the face of dynamic and plastic synaptic inputs. In the past decade, we have learned that neurons achieve this type of homeostatic regulation through a variety of ion channels, including K+ channels. It has also become clear that under certain pathological conditions, these homeostatic mechanisms provide neuroprotection. In this article, I will review recent advances in our understanding of K+ channel—mediated homeostatic regulation of neuronal excitability and discuss involvement of these channels in hyperexcitable diseases where they provide neuroprotection.