Molecular Human Reproduction, Vol. 7, No. 9, 819-828,
September 2001
© 2001 European Society of Human Reproduction and Embryology
Testis and spermatogenesis |
Effects of the ion-channel blocker quinine on human sperm volume, kinematics and mucus penetration, and the involvement of potassium channels
Institute of Reproductive Medicine of the University, Domagkstrasse 11, D-48129 Münster, Germany
Abstract
Sperm defects in the infertile c-ros knockout mouse model have recently highlighted the importance of volume regulation in sperm function. In this study, washed human spermatozoa were shown to change size and shape, as detected by flow cytometry and light microscopy, in response to the ion-channel blocker quinine (minimum effective doses at 20 and 125 µmol/l respectively). The increase in sperm volume was accompanied by reduced straight-line velocity (VSL) and linearity (LIN) of the swim-path but increased lateral head displacement and curvilinear velocity, while percentage motility was unaffected. Spermatozoa in semen and in artificial cervical mucus were similarly affected at 0.2 and 0.5 mmol/l quinine, resulting in marked reduction of mucus penetration and migration. The effects of quinine on sperm volume and kinematics were reduced or abolished by the K+-ionophores valinomycin (1 and 5 µmol/l) and gramicidin (0.5 and 1 µmol/l). In Ca2+-free medium; however, the quinine effects largely persisted. The K+-channel blocker, 4-aminopyridine (1 and 4 mmol/l), mimicked the quinine effects in the reduction of VSL and LIN, while the K+-channel blocker, tetraethylammonium chloride (TEA, 2.5–10 mmol/l), did not affect kinematics. The K+-channel (Kv1.3)-specific inhibitor, margatoxin, and the Ca2+-dependent K+-channel blocker, charybdotoxin, also had no effects. This study suggests that volume regulation in human spermatozoa and the linear trajectory of their motion may rely on quinine-sensitive and TEA-insensitive, largely calcium-independent, potassium channels, and possibly volume-sensitive organic anion channels. These channels could be targets for contraception.
infertility/K+ channel/regulatory volume decrease/sperm function/sperm motility
Notes
1To whom correspondence should be addressed. E-mail: yeung{at}uni-muenster.de
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