The role of connexin 43 in mediating odor response

Abstract

Connexin proteins are the hemichannels that form gap junctions to regulate the intercellular communication. Connexin 43 (Cx43) is the most common gap junction protein that expresses in many cell types, including the olfactory sensory neurons. Phosphorylation is a crucial step to regulate the function of Cx43. Gap junction was found to modulate the odor response, but the specific role is still elusive. Here, we report that gap junctions play a role in odor-evoked calcium response in both heterologous cell system and primary olfactory sensory neurons. This regulation is mediated through gap junction protein Cx43. Overexpression of full length Cx43 can counteract the inhibitory effect of gap junction or connexin blockers on odor-evoked [Ca2+]i increase in hana3A cells. Carboxy-terminal of Cx43 (Cx43CT) has the similar function as the full length of Cx43. Furthermore, we found that expression level of phosphorylation of Cx43 at S368 is dynamic with the stimulation of odor in hana3A cells. Expression level of phosphorylated Cx43 at S368 was decreased when gap junction or connexin inhibitors were applied. Phosphorylation of Cx43 during odor or inhibitor stimulation may be mediated by ERK and JNK signaling pathway. Altogether our data suggest that expression of Cx43 can regulate the odor response. This study provides a clue to indicate the possible protective mechanism of gap junction in odor response.