HCN Channel Targeting Drugs
Switching screenings from targeting Ih to Iinst channels
VCU researchers have developed a novel screening strategy for drugs that target HCN channels. HCN channels, often called pacemaker channels, contribute to a diverse number of physiological functions, including heart rate, pain sensation, as well as learning and memory. Blockers of HCN channels are able to regulate some of these processes, such as reducing heart rate, and have minimal side effects. Traditional screening methods for these drugs focus on the HCN channel which conducts the Ih current. However, the Iinst current could have a greater physiological effect due to its longer opening duration. As a result, our researchers have developed methods to change the conductance of the HCN channels from Ih to Iinst to investigate its potential applications.
Two different methods have been developed to convert the HCN channels from conducting Ih to Iinst. The first method, which involves photochemical transformation, leads to a permanent conversion of the channel. The second method, which involves physiological modifications, is completely reversible. These methods will not only allow for further understanding of the Iinst current, they will also allow for the drug screening of Iinst HCN channels. These drug screenings could lead to the discovery of a whole new family of drugs with clinical significance that may be more effective than the current Ih blockers.
In silico data is available.