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 hig hlighted the importance of volume regulation in sperm function. In this stu dy, washed human spermatozoa were shown to change size and shape, as detect ed by flow cytometry and light microscopy, in response to the ion-channel b locker quinine (minimum effective doses at 20 and 125 mu mol/l respectively ). The increase in sperm volume was accompanied by reduced straight-line ve locity (VSL) and linearity (LIN) of the swim-path but increased lateral hea d displacement and curvilinear velocity, while percentage motility was unaf fected. Spermatozoa in semen and in artificial cervical mucus were similarl y 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 a nd 5 mu mol/l) and gramicidin (0.5 and 1 mu mol/l). In Ca2+-free medium; ho wever, the quinine effects largely persisted. The K+-channel blocker, 4-ami nopyridine (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)-spec ific inhibitor, margatoxin, and the Ca2+-dependent K+-channel blocker, char ybdotoxin, 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, potassi um channels, and possibly volume-sensitive organic anion channels. These ch annels could be targets for contraception.