Molecular aspects of voltage-dependent ion channels.
Voltage-dependent ion channels appear to form a large family whose individual structures suggest a lineage to a common ancestral channel protein. These channels share the feature of having a number (usually four or five) of homologous subunits or homologous internal repeat domains. Each contains a positively charged amphipathic helix at a conserved location within each of these subunits or repeat domains; voltage-dependent gating may be a property of this conserved S4 helix. In each channel, the ion pore itself is thought to be formed by contributions from helices of each of the subunits or domains which are themselves disposed in a pseudosymmetrical fashion around the aqueous pore. In spite of these similarities, each channel type, as well as subtypes within each type, exhibit unique kinetic and pharmacological properties, and varying patterns of tissue and cellular expression. Presumably these unique aspects of channel function are contributed by the variable regions of the protein structure and in this regard the cytoplasmic loops connecting the repeat domains or the amino- and carboxy-termini of the individual subunits may play a particular role. An appreciation of both the common aspects of channel structure and the unique characteristics of the specific channel of interest will be useful in determining its contribution to the pathobiology of hypertension and in planning therapeutic approaches in which the channel may play a role.
Barchi
R L
RL
Mahoney Institute of Neurological Sciences, University of Pennsylvania School of Medicine, Philadelphia 19104.
D000595:Amino Acid Sequence; D000818:Animals; D015220:Calcium Channels / Q000737:chemistry; D007473:Ion Channels / Q000737:chemistry*; D008969:Molecular Sequence Data; D015221:Potassium Channels / Q000737:chemistry; D011487:Protein Conformation; D012689:Sequence Homology, Nucleic Acid; D015222:Sodium Channels / Q000737:chemistry
D015220:Calcium Channels; D007473:Ion Channels; D015221:Potassium Channels; D015222:Sodium Channels