PT  - JOURNAL ARTICLE
AU  - William A. Catterall
AU  - Teresa M. Swanson
TI  - Structural Basis for Pharmacology of Voltage-Gated Sodium and Calcium Channels
AID  - 10.1124/mol.114.097659
DP  - 2015 Jul 01
TA  - Molecular Pharmacology
PG  - 141--150
VI  - 88
IP  - 1
4099  - http://molpharm.aspetjournals.org/content/88/1/141.short
4100  - http://molpharm.aspetjournals.org/content/88/1/141.full
SO  - Mol Pharmacol2015 Jul 01; 88
AB  - Voltage-gated sodium channels initiate action potentials in nerve, muscle, and other electrically excitable cells. Voltage-gated calcium channels are activated by depolarization during action potentials, and calcium influx through them is the key second messenger of electrical signaling, initiating secretion, contraction, neurotransmission, gene transcription, and many other intracellular processes. Drugs that block sodium channels are used in local anesthesia and the treatment of epilepsy, bipolar disorder, chronic pain, and cardiac arrhythmia. Drugs that block calcium channels are used in the treatment of epilepsy, chronic pain, and cardiovascular disorders, including hypertension, angina pectoris, and cardiac arrhythmia. The principal pore-forming subunits of voltage-gated sodium and calcium channels are structurally related and likely to have evolved from ancestral voltage-gated sodium channels that are widely expressed in prokaryotes. Determination of the structure of a bacterial ancestor of voltage-gated sodium and calcium channels at high resolution now provides a three-dimensional view of the binding sites for drugs acting on sodium and calcium channels. In this minireview, we outline the different classes of sodium and calcium channel drugs, review studies that have identified amino acid residues that are required for their binding and therapeutic actions, and illustrate how the analogs of those key amino acid residues may form drug-binding sites in three-dimensional models derived from bacterial channels.