Blockade of epithelial sodium channels improves sperm motility in asthenospermia patients

Epithelial Na(+) channels (ENaCs) are ion channels that play important roles in physiology as well as pathophysiology. Inhibiting ENaCs using amiloride and its derivatives has been suggested in treatment of cardiovascular disease and hypertension. By immunoblotting, we demonstrated the presence of ENaC-alpha protein in the flagellar midpiece of both rat and human sperm. Immunohistochemistry analyses in rat testis localized ENaC-alpha expressed in the Leydig cell, Sertoli cell, Ap spermatogonium, spermatocyte, spermatid and residual body. Importantly, using computer-assisted sperm motility analysis, we first observed that EIPA [5-(N-ethyl-N-isopropyl)-amiloride hydrochloride] inhibition of ENaCs, possibly including ENaC-alpha and ENaC-delta, significantly improved the sperm motility in healthy donors by 14.23% (mean +/- SEM, 68.75 +/- 9.76% vs. 78.53 +/- 6.20%, p < 0.001) and in asthenospermia patients by 115.89% from 9.50 +/- 6.11% to 20.51 +/- 12.13% (mean +/- SEM, p < 0.001). The improved sperm motility by EIPA has important clinical implications in the treatment of asthenospermia and certainly warrants further investigation.