Role of NBC cotransporter in the PKA-dependent regulation of membrane potential during human sperm capacitation

PINTO, NICOLAS A.; LUQUE, GUILLERMINA; TREVIÑO, CLAUDIA L.; PUGA MOLINA, LIS C.; TORRES RODRÍGUEZ, PAULINA; TORRES, NICOLAS; GILIO, N.; ROMAROWSKI, ANA; BUFFONE, MARIANO G.; DARSZON, ALBERTO

Conferencia; Holderness, NH, USA; 2017

At ejaculation, mature sperm are not able to fertilize an oocyte. They require to spend a limited period of time in the female reproductive tract and undergo several maturational changes, all grouped under the name of capacitation. From a molecular point of view, one of the first events that occur during capacitation is a HCO3--dependent activation of the atypical soluble adenylyl cyclase ADCY10 which leads to cAMP synthesis and the subsequent activation of PKA. Capacitation is also accompanied by hyperpolarization of the sperm plasma membrane. We previously observed that PKA and CFTR activity are both necessary for membrane potential (Em)Em regulation. Because CFTR phosphorylation by PKA is mandatory for the function of the channel. we investigated the initial HCO3- transport and how PKA modulates Em changes during capacitation. In the present work we have found that the activity of the Na+/HCO3- cotransporter (NBC) affects PKA activity and its relationship with ENaC channel and membrane potentialwe observed that inhibition of NBC reduced the HCO3- influx resulting in lower PKA activity and that this inhibitory effect can be recovered by cAMP permeable analogs or by direct inhibition of ENaC. This results suggest that NBC is upstream PKA and ENaC activity in the modulation of Em during human sperm capacitation.