The Study Of Blocking Effect Of ZD7288on Sodium Channel

Hyperpolarization-activated cyclic nucleotide-gated channels (HCN channels) isknown as pacemaker channel, which contributes to firing of action potential and normalbalance function. It is widely distributed in nerve system and heart. It also plays animportant role in neuropathic pain. For the function study of HCN channels, ZD7288hasbeen widely used as a blocker of the channel to test the relationships between HCNchannels and heart and brain function. ZD7288is widely considered as a selective blockerof HCN currents. Although research shows that ZD7288also inhibits T-type calciumchannel, but the effect is based on high concentration, which makes the discovery a hotspot. ZD7288inextricably linked with HCN channels in HCN channel function studies. Inorder to understand the body’s response to the blocked HCN channels, most researchersuse ZD7288to block HCN channel. However, during our research, we found that ZD7288inhibits not only HCN channel currents and T-type calcium channel, but also sodiumchannel in DRG neurons, and the blocking effect is more obvious than that of HCNchannel, which is reflected in the IC50and the pharmacodynamics. Another differencebetween the blocking effect of two channels is that when blocking sodium channel, theblocking effect can wash out easily, however, when it comes to HCN channel, the effectcan’t wash out within ten minutes. We also confirmed that ZD7288inhibits sodiumchannel current in HEK293cells transfected with Nav1.4plasmids. Thus our findingschallenge the view that ZD7288is a selective blocker of HCN channels. Therefore,conclusions about the role of HCN channels in neuronal function should be re-evaluated ifthey are drawn based exclusively on the effect of ZD7288.