Extracellular K⁺ and astrocyte signaling via connexin and pannexin channels

Astrocytes utilize two major pathways to achieve long distance intercellular communication. One pathway involves direct gap junction mediated signal transmission and the other consists of release of ATP through pannexin channels and excitation of purinergic receptors on nearby cells. Elevated extracellular potassium to levels occurring around hyperactive neurons affects both gap junction and pannexin1 channels. The action on Cx43 gap junctions is to increase intercellular coupling for a period that long outlasts the stimulus. This long term increase in coupling, termed "LINC", is mediated through calcium and calmodulin dependent activation of calmodulin dependent kinase (CaMK). Pannexin1 can be activated by elevations in extracellular potassium through a mechanism that is quite different. In this case, potassium shifts activation potentials to more physiological range, thereby allowing channel opening at resting or slightly depolarized potentials. Enhanced activity of both these channel types by elevations in extracellular potassium of the magnitude occurring during periods of high neuronal activity likely has profound effects on intercellular signaling among astrocytes in the nervous system.