Neuroglial potassium channels in health and disease

Abstract

Astrocytes are glial cells that contain a set of significant roles in maintaining the optimal conditions for the intercellular communications and functions in the central nervous system (CNS). They are essential for the control of extracellular ion homeostasis, neurotransmitter concentration, water balance and the support of the blood-brain barrier. Glial cells show a hyperpolarized membrane potential with a high K+ conductance, implicating the importance of potassium channels in these cells. The inwardly rectifying potassium channel (Kir) expressed in glial cells has the basic function in setting the cell membrane potential which regulates the transmembrane gradients of glutamate and other neurotransmitters, as well as of transported molecules. Through the mechanism of potassium buffering, astrocytes take up excess K+, siphon it towards sites with lower concentrations providing the equilibrium K+ concentration in the extracellular environment. Kir4.1 has the major role in spatial buffering and it is mainly expressed in astrocytes in CNS. It was revealed that other glial cells also express Kir4.1 with the role in maintaining membrane potential, cellular development and physiology.Two-pore domain K+ channels (K2P) TWIK-1 and TREK-1 were showed to play a part in astrocytic K+ passive conductance, although recent knockdown studies challenge these findings. Alterations in the expression and function of potassium channels are shown in many deleterious neural conditions. A reduced expression of Kir4.1 has been shown in amyotrophic lateral sclerosis, Alzheimer;'s disease, and Huntington disease. Antibodies against Kir4.1 were found in the serum of patients with multiple sclerosis. Cells with a decreased Kir4.1 expression show a significant cell membrane depolarization and impaired K+ and glutamate uptake that lead to long term CNS dysfunction. Recent studies on K2Ps revealed an important role for TWIK-1 and TREK-1 in glutamatergic synaptic transmission and thus their potential involvement in glutamate release could affect pathological conditions. Changes in K+ channels in different CNS pathologies could imply common underlying mechanisms of neurodegeneration. In this review, based on our and the studies of others, we will also discuss Kir4.1/AQP4 complex and its significance in keeping water and ion balance in physiological and pathophysiological conditions.