ZD7288 inhibits low-threshold Ca(2+) channel activity and regulates sperm function.
In this study, ZD7288, a blocker of hyperpolarization-activated and cyclic nucleotide-gated (HCN) channels, has been found to inhibit the mouse sperm acrosome reaction (AR). HCN channels have not yet been either recorded or implicated in mouse sperm AR, but low-threshold (T-type) Ca(2+) channels have. Interestingly, ZD7288 blocked native T-type Ca(2+) currents in mouse spermatogenic cells with an IC(50) of about 100 microM. This blockade was more effective at voltages producing low levels of inactivation, suggesting a differential affinity of ZD7288 for different channel conformations. Furthermore, ZD7288 inhibited all cloned T-type but not high-threshold N-type channels heterologously expressed in HEK-293 cells. Our results further support the role of T-type Ca(2+) channels in the mouse sperm AR.
Felix
Ricardo
R
Department of Physiology, Biophysics and Neuroscience, Cinvestav-IPN, Mexico City, Mexico.
Sandoval
Alejandro
A
Sánchez
Daniel
D
Gómora
Juan Carlos
JC
De la Vega-Beltrán
José L
JL
Treviño
Claudia L
CL
Darszon
Alberto
A
D020101:Acrosome Reaction / Q000187:drug effects; D000818:Animals; D020747:Calcium Channels, T-Type / Q000187:drug effects* / Q000502:physiology*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006801:Humans; D015640:Ion Channel Gating / Q000187:drug effects* / Q000502:physiology*; D007668:Kidney / Q000187:drug effects / Q000502:physiology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D011743:Pyrimidines / Q000494:pharmacology*; D013094:Spermatozoa / Q000187:drug effects* / Q000502:physiology*
D020747:Calcium Channels, T-Type; D011743:Pyrimidines; C082246:ICI D2788