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) Ca2+ channels have. Interestingly, ZD7288 blocked native T-type Ca2+ currents in mouse spermatogenic cells with an IC50 of about 100 muM. 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 Ca2+ channels in the mouse sperm AR. (C) 2003 Elsevier Inc. All rights reserved.