Question:

Studies using ion sensitive dyes have shown that progesterone evokes Ca²⁺ and Na⁺ entry in human spermatozoa (Parat et al. Bio Reprod 66, 1775-80: 2002). However, the biophysical properties of progesterone activated channels are unknown.

Method:

Membrane currents were recorded from human spermatozoa (normal volunteers) by whole cell recording (Kirichock et al. Nature 439, 737-740: 2006) under quasi-physiological ionic conditions.

Results:

Analysis of the currents evoked by depolarising voltage ramps (-92 to 68mV, 5 seconds) showed that progesterone (500nM) had no effect upon the voltage-induced outward K⁺ currents characteristically seen under quasi-physiological conditions. However, repolarisation to -92mV consistently evoked a tail current (I_Tail) and selectively increasing [Na⁺]_o, [K⁺]_o or [Ca²⁺]_o all augmented the magnitude of this current indicating that the underlying ion channels are permeable to Na⁺, K⁺ and Ca²⁺. Moreover, the application of progesterone (500nM) augmented I_Tail from -12.96 ± 0.97 pA/pF to -20.29 ± 1.03 pA/pF (n = 6, p< 0.001) over a 24-30 second period. It is therefore clear that this hormone augments the activity of this voltage-induced cation conductance. In subsequent experiments the current quantified at 2 mM [Ca²⁺]_o under standard ionic conditions ([K⁺]_o = 3mM, [Na⁺]_o = 26mM) was subtracted from the current measured at 10 mM [Ca²⁺]_o in order to assess the voltage-induced Ca²⁺ current (I_Ca). Progesterone augmented I_Ca from -13.9 ± 2.9 pA/pF to -26.4 ± 3.5 pA/pF (n = 6, p< 0.01).

Conclusion:

Progesterone evokes a cation current in human spermatozoa under quasi-physiological conditions.