title: Fenvalerate modifies T-type Ca2+ channels in mouse spermatogenic cells.
abstract: Prior to fertilization sperm must undergo the acrosome reaction that is initiated by opening of T-type Ca(2+) channel. Hence, T-type Ca(2+) channels could be a potential target for agents affecting the acrosome reaction. Our previous data have suggested that fenvalerate, a type II pyrethroid, inhibited the acrosome reaction in mice. To elucidate its potential mechanism we investigated fenvalerate's effect on T-type Ca(2+) channels in mouse pachytene spermatocytes using a whole-cell patch clamp technique. Fenvalerate significantly inhibited T-type Ca(2+) currents in a concentration-dependent manner. The maximal inhibitory concentration was 1 microM. The inhibitory effect of fenvalerate was slow and irreversible after washout of the drug. The curves of activation and inactivation simultaneously shifted to hyperpolarization, about 14 mV, suggesting the open time of Ca(2+) channel was unchanged. Voltage-dependent gating of Ca(2+) channel indicated a change in permeability to ions that contributed to fenvalerate's inhibition on Ca(2+) current. Taken together with our previous findings, these data suggest that the changes of T-type Ca(2+) currents contribute to the suppression of acrosome reaction and fertilizing ability caused by fenvalerate.
authors.affiliation: Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing, Jiangsu, 210029, PR China. hxiao@njmu.edu.cn
authors.forename: Hang
authors.initials: H
authors.lastname: Xiao
authors.forename: Xi-Chun
authors.initials: XC
authors.lastname: Zhang
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.forename: Xiao-Qing
authors.initials: XQ
authors.lastname: Dai
authors.forename: Wei
authors.initials: W
authors.lastname: Gong
authors.forename: Jie
authors.initials: J
authors.lastname: Cheng
authors.forename: Rong
authors.initials: R
authors.lastname: Gao
authors.forename: Xinru
authors.initials: X
authors.lastname: Wang
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D020747:Calcium Channels, T-Type / Q000187:drug effects* / Q000502:physiology; D008297:Male; D051379:Mice; D009570:Nitriles / Q000633:toxicity*; D018408:Patch-Clamp Techniques; D011722:Pyrethrins / Q000633:toxicity*; D013090:Spermatocytes / Q000187:drug effects* / Q000502:physiology
chemical_list: D020747:Calcium Channels, T-Type; D009570:Nitriles; D011722:Pyrethrins; D002118:Calcium; C017690:fenvalerate