Interaction between nitric oxide signaling and gap junctions during ischemic preconditioning: Importance of S-nitrosylation vs. protein kinase G activation.

Much effort has been dedicated to exploring the mechanisms of IPC, and the GJ is one of the proposed targets of IPC. Several lines of evidence have indicated that NO affects GJ permeability regulation and expression of connexin isoforms. NO-induced stimulation of the sGC-cGMP pathway and the subsequent PKG activation could lead directly to connexin phosphorylation and GJ coupling modification. Additionally, because NO-induced cardioprotection against I/R injury beyond the cGMP/PKG-dependent pathway has been reported in isolated cardiomyocytes, it has been posited that NO-mediated GJ coupling might be independent from the activation of the NO-induced cGMP/PKG pathway during IPC. S-nitrosylation by NO exerts a major influence in IPC-induced cardioprotection. It has been suggested that NO-mediated cardioprotection during IPC was not dependent on sGC/cGMP/PKG but on SNO signaling. We need more researches to prove that which signaling pathway (S-nitrosylation or protein kinase G activation) is the major one modulating GJ coupling during IPC. The aim of review article is to discuss the possible signaling pathways of NO in regulating GJ during IPC.