title: Ligand action on sodium, potassium, and calcium channels: role of permeant ions.
abstract: Ion channels are targets for many naturally occurring toxins and small-molecule drugs. Despite great progress in the X-ray crystallography of ion channels, we still do not have a complete understanding of the atomistic mechanisms of channel modulation by ligands. In particular, the importance of the simultaneous interaction of permeant ions with the ligand and the channel protein has not been the focus of much attention. Considering these interactions often allows one to rationalize the highly diverse experimental data within the framework of relatively simple structural models. This has been illustrated in earlier studies on the action of local anesthetics, sodium channel activators, as well as blockers of potassium and calcium channels. Here, we discuss the available data with a view to understanding the use-, voltage-, and current carrying cation-dependence of the ligand action, paradoxes in structure--activity relationships, and effects of mutations in these ion channels.
authors: Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, L8S 4K1, Canada. zhorov@mcmaster.ca
authors: Boris S
authors: BS
authors: Zhorov
authors: Denis B
authors: DB
authors: Tikhonov
mesh_terms: D002120:Calcium Channel Agonists / Q000737:chemistry / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000737:chemistry / Q000494:pharmacology; D015220:Calcium Channels / Q000737:chemistry / Q000378:metabolism*; D002412:Cations / Q000378:metabolism; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D058990:Molecular Targeted Therapy / Q000379:methods; D026902:Potassium Channel Blockers / Q000737:chemistry / Q000494:pharmacology; D015221:Potassium Channels / Q000819:agonists / Q000737:chemistry / Q000378:metabolism*; D062687:Sodium Channel Agonists / Q000737:chemistry / Q000494:pharmacology; D026941:Sodium Channel Blockers / Q000737:chemistry / Q000494:pharmacology; D015222:Sodium Channels / Q000737:chemistry / Q000378:metabolism*; D013329:Structure-Activity Relationship; D014118:Toxins, Biological / Q000737:chemistry / Q000494:pharmacology
chemical_list: D002120:Calcium Channel Agonists; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D002412:Cations; D008024:Ligands; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D062687:Sodium Channel Agonists; D026941:Sodium Channel Blockers; D015222:Sodium Channels; D014118:Toxins, Biological