Structural basis of voltage-gated K+ channel pharmacology.

Major advances have been made in understanding the domains and amino acid sidechains important for the function of voltage-gated K+ channels, by combining recombinant DNA techniques with pharmacological and electrophysiological approaches. As explained in this review by Olaf Pongs, the results of these experiments have enabled description of a detailed model of the K+ channel pore structure and provide an exciting picture of how open-channel blockers occlude the pore of K+ channels. Since the pore is a highly conserved structure among voltage-gated K+ channels, there are only limited possibilities for open K+ channel blockers to distinguish between the many distinct voltage-gated K+ channels, which have diverse kinetic and conductance properties.