Structure, function and expression of voltage-dependent sodium channels.
Voltage-dependent sodium channels control the transient inward current responsible for the action potential in most excitable cells. Members of this multigene family have been cloned, sequenced, and functionally expressed from various tissues and species, and common features of their structure have clearly emerged. Site-directed mutagenesis coupled with in vitro expression has provided additional insight into the relationship between structure and function. Subtle differences between sodium channel isoforms are also important, and aspects of the regulation of sodium channel gene expression and the modulation of channel function are becoming topics of increasing importance. Finally, sodium channel mutations have been directly linked to human disease, yielding insight into both disease pathophysiology and normal channel function. After a brief discussion of previous work, this review will focus on recent advances in each of these areas.
Kallen
R G
RG
Mahoney Institute of Neurological Sciences, University of Pennsylvania School of Medicine, Philadelphia.
Cohen
S A
SA
Barchi
R L
RL
D000200:Action Potentials; D000595:Amino Acid Sequence; D000818:Animals; D001923:Brain Chemistry; D002874:Chromosome Mapping; D017868:Cyclic AMP-Dependent Protein Kinases / Q000502:physiology; D005786:Gene Expression Regulation; D006321:Heart / Q000502:physiology; D015640:Ion Channel Gating / Q000502:physiology; D007700:Kinetics; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009124:Muscle Proteins / Q000737:chemistry / Q000187:drug effects / Q000502:physiology; D016296:Mutagenesis; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000187:drug effects / Q000502:physiology; D009468:Neuromuscular Diseases / Q000503:physiopathology; D009498:Neurotoxins / Q000494:pharmacology; D010766:Phosphorylation; D011487:Protein Conformation; D011499:Protein Processing, Post-Translational; D017434:Protein Structure, Tertiary; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000502:physiology; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D015222:Sodium Channels / Q000737:chemistry / Q000187:drug effects / Q000502:physiology*
D009124:Muscle Proteins; D009419:Nerve Tissue Proteins; D009498:Neurotoxins; D011993:Recombinant Fusion Proteins; D015222:Sodium Channels; D017868:Cyclic AMP-Dependent Protein Kinases