HCN channels as targets for drug discovery.
Hyperpolarization- and Cyclic Nucleotide-gated (HCN) channels are a family of six transmembrane domain, single pore-loop, hyperpolarization activated, non-selective cation channels. The HCN family consists of four members (HCN1-4). HCN channels represent the molecular correlates of I(h) (also known as 'funny' I(f) and 'queer' I(q)), a hyperpolarization-activated current best known for its role in controlling heart rate and in the regulation of neuronal resting membrane potential and excitability. A significant body of molecular and pharmacological evidence is now emerging to support a role for these channels in the function of sensory neurons and pain sensation, particularly pain associated with nerve or tissue injury. As such, HCN channels may represent valid targets for novel analgesic agents. This evidence will be reviewed in this article. We will then summarize our efforts to develop and validate methods for screening for novel HCN channel blockers.
Maher
Michael P
MP
Johnson & Johnson Pharmaceutical Research and Development, L.L.C., San Diego, CA 92121, USA.
Wu
Nyan-Tsz
NT
Guo
Hong-Qing
HQ
Dubin
Adrienne E
AE
Chaplan
Sandra R
SR
Wickenden
Alan D
AD
D000700:Analgesics / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D054815:Cyclic Nucleotide-Gated Cation Channels / Q000187:drug effects*; D016503:Drug Delivery Systems; D055808:Drug Discovery / Q000379:methods*; D004353:Drug Evaluation, Preclinical / Q000379:methods; D006801:Humans; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D015221:Potassium Channels / Q000187:drug effects*
D000700:Analgesics; D054815:Cyclic Nucleotide-Gated Cation Channels; C578665:HCN1 protein, human; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D015221:Potassium Channels