Effects of the ion-channel blocker quinine on human sperm volume, kinematics and mucus penetration, and the involvement of potassium channels.
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 micromol/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 micromol/l) and gramicidin (0.5 and 1 micromol/l). In Ca(2+)-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 Ca(2+)-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.
Yeung
C H
CH
Institute of Reproductive Medicine of the University, Domagkstrasse 11, D-48129 Münster, Germany. yeung@uni-muenster.de
Cooper
T G
TG
D002118:Calcium / Q000378:metabolism; D002412:Cations / Q000378:metabolism; D048429:Cell Size / Q000187:drug effects; D002582:Cervix Mucus / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006801:Humans; D007476:Ionophores / Q000378:metabolism; D008297:Male; D009994:Osmolar Concentration; D010042:Ouabain / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000502:physiology*; D011803:Quinine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D012661:Semen / Q000737:chemistry; D013081:Sperm Motility / Q000187:drug effects*; D013084:Sperm-Ovum Interactions / Q000187:drug effects*
D002412:Cations; D004791:Enzyme Inhibitors; D007476:Ionophores; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D010042:Ouabain; D011803:Quinine; D011188:Potassium; D002118:Calcium