Antagonists of neuronal calcium channels: structure, function, and therapeutic implications.
This article reviews the structural and functional diversity of neuronal calcium channels and the therapeutic potential of antagonizing such channels. Through spatial and temporal control of intracellular calcium concentration, voltage-sensitive calcium channels regulate a host of neuronal processes, including neurotransmitter secretion, electrical activity, cytoskeletal function, cell metabolism and proliferation, and gene expression. Several genes elaborate a number of calcium channel isoforms or subtypes--each tailored to specific roles in neuronal function and possessing distinct biophysical properties, distribution, modulation, and pharmacological sensitivity. This diversity has raised the possibility that subtype-specific antagonists could provide novel treatments for some neuropathologies. In fact, neuroprotective and analgesic actions of N-type channel blockers in animals appear to confirm this supposition. These properties prompted human clinical studies evaluating these agents for prevention of neuronal degeneration following ischemic brain trauma and for relief of pain. Future medical applications for these blockers and antagonists of other channels subtypes are discussed.
Miljanich
G P
GP
Neurex Corporation, Menlo Park, California 94025-1012, USA.
Ramachandran
J
J
D000595:Amino Acid Sequence; D000698:Analgesia; D000818:Animals; D001327:Autoimmune Diseases / Q000175:diagnosis; D002545:Brain Ischemia / Q000188:drug therapy; D002121:Calcium Channel Blockers / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D015220:Calcium Channels / Q000737:chemistry / Q000502:physiology*; D006801:Humans; D006973:Hypertension / Q000188:drug therapy; D008969:Molecular Sequence Data; D009422:Nervous System Diseases / Q000188:drug therapy*; D009474:Neurons / Q000187:drug effects* / Q000502:physiology
D002121:Calcium Channel Blockers; D015220:Calcium Channels