Membrane potential and feedback dynamics regulate CatSper-mediated progesterone signaling in human sperm

Area of Science:

• Human reproductive biology
• Sperm physiology
• Ion channel function

Background:

• Progesterone-induced calcium (Ca²⁺) signals in human sperm are vital for fertilization.
• The precise mechanisms regulating these Ca²⁺ signals remain unclear.

Purpose of the Study:

• To investigate how progesterone influences human sperm membrane potential (V_m).
• To elucidate the mechanisms controlling progesterone-induced Ca²⁺ signaling.

Main Methods:

• Quantitative kinetic fluorimetry using voltage-sensitive fluorescent indicators.
• FAST^M technique for simultaneous millisecond-resolution recording of V_m and intracellular Ca²⁺.
• Investigated the roles of CatSper and Slo3 ion channels.

Main Results:

• Progesterone triggers a rapid pulse-like depolarization and repolarization of sperm V_m.
• CatSper-mediated Ca²⁺ influx causes depolarization, while V_m/Ca²⁺-dependent feedback and Slo3-mediated K⁺ efflux promote repolarization.
• Identified a dynamic interplay between CatSper and Slo3 in regulating V_m.

Conclusions:

• Non-genomic progesterone signaling in human sperm involves negative feedback on CatSper.
• The study reveals a dynamic interplay between CatSper and Slo3 channels in controlling V_m.
• Novel kinetic V_m recording techniques offer new avenues for studying CatSper-mediated Ca²⁺ signaling.