Pharmacology of hSlo3 channels and their contribution in the capacitation-associated hyperpolarization of human sperm

Slo3 channels (mSlo3) primarily mediate mouse sperm K+ currents and are essential for the capacitation-associated hyperpolarization (CAH). Whether Slo3 and/or Slo1, two Slo family K+ channels are functionally expressed in human sperm is controversial. Our recent pharmacological studies of the human sperm CAH suggested the participation of both. Lack of a detailed pharmacology of heterologously expressed human Slo3 (hSlo3) prevented precisely identifying the K+ channel(s) involved. In the present report, we compare the pharmacological profile of expressed hSlo3 in CHO cells with that of the CAH to advance this matter. Whole-cell patch-clamp recordings showed that hSlo3 currents are inhibited: significantly by progesterone, Ba2+ and quinidine; partially by Penitrem A and Charybdotoxin; and poorly by Iberiotoxin and Slotoxin. Surprisingly, hSlo3 currents were resistant to Clofilium and 60 mM TEA+ which inhibit mSlo3. Pharmacological comparison of the CAH and hSlo3 profiles indicates in addition to hSlo3, other K+ channels, possibly Slo1, may participate in CAH. The pharmacological profile of heterologously expressed hSlo3 channels differs from that of mSlo3 K+ channels, consistent with species-specific differences observed among other sperm ion channels. While the pharmacological correlation analysis of the hSlo3 currents and the CAH confirmed the participation of hSlo3 channels, it suggests that additional K+ channels may be involved, in particular Slo1 channels.