Figure 8.

Proposed model for the role of Cx43 in preconditioning. Cx43 hemichannels are, after synthesis, transported from the Golgi to the plasma membrane. After insertion in the plasma membrane, Cx43 remains as hemichannels or hemichannels are either recruited into gap-junction plaques or endocytosed for degradation. Preconditioning reduces lysosomal degradation, resulting in reinsertion of endosomes containing Cx43 in the plasma membrane. In turn, the increased number of plasma membrane hemichannels leads to increased ATP release, resulting in accumulation of adenosine. Adenosine is a potent neuroprotective agent that reversibly inhibits excitatory transmission and thereby reduces excitotoxic neuronal injury.