Question:

What are the biophysical properties of the K⁺ channels in human spermatozoa?

Method:

Membrane currents were recorded from human spermatozoa (normal volunteers) by whole cell recording (Kirichok et al. Nature 439, 737-740: 2006).

Results:

Depolarization evoked outward K⁺ current under physiological ionic conditions and, since half-maximal activation occurred at 26.1 ± 4.6 mV, the underlying channels display weak dependence upon V_m. This K⁺ current was blocked (>85%) by quinidine (0.3 mM), bupivacaine (3 mM) and clofillium (50 µM) but unaffected by 4-amino pyridine (4-AP, 2 mM). Replacing pipette K⁺ with NMDG⁺ abolished the voltage-induced current but small (~10%) responses to depolarization persisted if K⁺ was replaced with Na⁺. Since these outward Na⁺ currents displayed the same pharmacological profile as the K⁺ current (> 85% block with 0.3 mM quinidine, 3.0 mM bupivacaine and 50 µM clofillium, unaffected by 2 mM 4-AP), depolarization appears to activate channels with poor (~5 fold) K⁺ / Na⁺ selectivity. Monovalent cations can permeate CatSper, especially in the absence of Ca²⁺ / Mg²⁺ (Lishko et al. Nature 471, 387 - 392: 2011; Zeng et al. Proc Natl Acad Sci U S A 108, 5879-5884), and current flow via this channel (Lishko et al. Nature 471, 387 - 392: 2011) was also blocked (>85%) by quinidine (0.3 mM), bupivacaine (3 mM) and clofillium (50 µM) but not 4-AP (2 mM). Moreover, CatSper blockers (2 µM NNC55-0396, 30 µM mibefradil) blocked the voltage-induced K⁺ current and depolarised V_m.

Conclusion:

Hyperpolarizing K⁺ currents in human spermatozoa may flow via CatSper.