Prospects for rational development of pharmacological gap junction channel blockers.
Connexin-null mice and human genetic gap junction diseases illustrate the important roles that gap junction channels play under normal conditions, and the neuro- and cardioprotective effects of gap junction blocking agents demonstrate that closure of these channels may be beneficial in certain pathological situations. This overview summarizes studies in which gap junction modifying reagents have been characterized, highlighting examples of agents for which selectivity for gap junction subtypes has been demonstrated. In addition, strategies for targeting connexin domains through peptide inhibitors are outlined, which may ultimately provide agents that are not only connexin-selective in their actions, but also affect only a subset of a gap junction channel's gating responses.
Spray
David C
DC
Department of Neuroscience, Albert Einstein College of Medicine, Bronx, New York 10461, USA. spray@aecom.yu.edu
Rozental
Renato
R
Srinivas
Miduturu
M
D000818:Animals; D017630:Connexins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016503:Drug Delivery Systems / Q000379:methods*; D017629:Gap Junctions / Q000378:metabolism; D006801:Humans; D007473:Ion Channels / Q000037:antagonists & inhibitors* / Q000378:metabolism
D017630:Connexins; D007473:Ion Channels