Abstract
Complexes formed with α5-integrins and the voltage-gated potassium (K+ ) channel KCNB1 (Kv2.1), known as IKCs, transduce the electrical activity at the plasma membrane into biochemical events that impinge on cytoskeletal remodeling, cell differentiation, and migration. However, when cells are subject to stress of oxidative nature IKCs turn toxic and cause inflammation and death. Here, biochemical, pharmacological, and cell viability evidence demonstrates that in response to oxidative insults, IKCs activate an apoptotic Mitogen-activated protein kinase/extracellular signal-regulated kinase (Ras-MAPK) signaling pathway. Simultaneously, wild-type (WT) KCNB1 channels sequester protein kinase B (Akt) causing dephosphorylation of BCL2-associated agonist of cell death (BAD), a major sentinel of apoptosis progression. In contrast, IKCs formed with C73A KCNB1 variant that does not induce apoptosis (IKCC73A ), do not sequester Akt and thus are able to engage cell survival mechanisms. Taken together, these data suggest that apoptotic and survival forces co-exist in IKCs. Integrins send death signals through Ras-MAPK and KCNB1 channels simultaneously sabotage survival mechanisms. Thus, the combined action of integrins and KCNB1 channels advances life or death.