Potential role of NBC cotransporter in the CFTR-dependent regulation of Em during human sperm capacitation

PUGA MOLINA LC; TORRES NI; TREVIÑO C; SANCHEZ O; PINTO NA; LUQUE GM; GILIO N; DARSZON A; BUFFONE MG

Rehovot

Congreso; The Batsheva de Rothschild Seminar on Challenges and Frontiers in Mammalian Reproduction; 2016

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 activation is necessary for CFTR activity and for modulation of Em changes. However, the main transporters involved in HCO3- initial transport and PKA-dependent Em changes are not well established. In the present work we have analyzed how the activity of CFTR regulates membrane potential during capacitation and its relationship with NBC and ENaC transporters. We observed that inhibition of both CFTR and NBC affected HCO3- influx resulting in lower PKA activity and that cAMP/PKA-downstream events are essential for the regulation of membrane potential.