Agonism and antagonism in cyclic nucleotide-gated channels

点击翻译按钮获取中文摘要

Cells control their life processes by producing natural chemical compounds (messengers) that bind to specific receptor proteins; in response, the receptors change their molecular structure in order to activate a particular biological function. Many physiological disorders, such as cancer and heart disease which afflict millions of Canadians, could be fought by artificial messengers (drugs) that either stimulate or suppress the ON- and OFF-switching of a specific receptor. My lab studies certain receptors called ion channels whose ON-conformation produces an electric current, so we can observe ON- and OFF-switching directly. We study a number of different ion channels, all of which respond to one type of messenger called cyclic nucleotide; this messenger is generated by the body under conditions of excitation, such as the "fight-or-flight" adrenaline rush, or during epileptic seizures in some parts of the brain. The molecules that form these ion channels all contain a specific sensing-domain which is the site for binding cyclic nucleotide. This sensing-domain obviously helps ON-switching after cyclic nucleotide is bound, but our lab has discovered that in different kinds of channels, the sensing-domain can do much more! For instance, in some channels, the sensing-domain will push the receptor OFF after being ON.