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HCN Channel as Therapeutic Targets for Heart Failure and Pain.

Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels play important roles both in the control of heart rate and neuronal excitability. HCN channels open on hyperpolarization voltage, permeate to potassium and sodium, and generate an inward current, which is modulated by intracellular cAMP. HCN channels have been reported to involve in various human diseases, including heart failure, pain and epilepsy with datas from mutagenesis, transgenic mice and pharmacological studies. As a result, HCN channels may offer excellent drug development opportunities for novel analgestic, bradycardic and anticonvulsant drugs. Ivabradine is the first HCN channel inhibitor being clinically approved in 2005 for the treatment of chronic stable angina pectoris and heart failure. This review will summarize the structure and function of HCN channels. Further, we will discuss recent advances concerning the identification and action mechanism of reported HCN channel inhibitors.