Figure 1.

General representation of the connexins (Cxs)-based channels and hemichannels participation in seizures and epilepsy, through synergistic actions of neuroinflammation and hyper excitability and synchronization. Different types of insults can produce seizures that modify intracellular pH, which opens hemichannels in glial cells (activated microglia and astrocytes), with the consequent calcium-dependent release of gliotransmitters (Glutamate Glu, D-serine, NAD and ATP) and proinflammatory molecules (NLRP-3 inflammasome: Caspase 1, IL-1β, IL18) that lead to neuroinflammation and open Cxs-based hemichannels. This last action is also facilitated by reactive oxygen species (ROS) and reactive nitrogen species (NOS) produced during seizures. In the same way, astrocytes can reinforce seizures through the opening of Cxs-based channels that activate a calcium wave in an astroglial syncytium that propagates excitability. In neurons, the opening of channels increases abnormal high excitability and synchronization that reinforces the cycle of seizures generation.