The potassium channel subunit Kvβ3 interacts with pannexin 1 and attenuates its sensitivity to changes in redox potentials

Pannexin 1 (Panx1), a member of the second gap junction protein family identified in vertebrates, appears to preferentially form non-junctional membrane channels. A candidate regulatory protein of Panx1 is the potassium channel subunit Kv beta 3, previously identified by bacterial two-hybrid strategies. Here, we report on the physical association of Panx1 with Kv beta 3 by immunoprecipitation when co-expressed in a neuroblastoma cell line (Neuro2A). Furthermore, in vivo co-expression of Panx1 and Kv beta 3 was shown to occur in murine hippocampus and cerebellum. Kv beta 3 is known to accelerate inactivation of otherwise slowly inactivating potassium channels under reducing conditions. We subsequently found that Panx1 channel currents exhibit a significant reduction when exposed to reducing agents, and that this effect is attenuated in the presence of Kv beta 3. Apparently, Kv beta 3 is involved in regulating the susceptibility of Panx1 channels to redox potential. Furthermore, the Panx1 channel blockers carbenoxolone and Probenecid were less effective in inhibiting Panx1 currents when Kv beta 3 was co-expressed. The influence of Kv beta 3 on Panx1 is the first example of modulation of Panx1 channel function(s) by interacting proteins, and suggests the physiological importance of sensing changes in redox potentials.