A functional connection between the pores of distantly related ion channels as revealed by mutant K+ channels.
The overall sequence similarity between the voltage-activated K+ channels and cyclic nucleotide-gated ion channels from retinal and olfactory neurons suggests that they arose from a common ancestor. On the basis of sequence comparisons, mutations were introduced into the pore of a voltage-activated K+ channel. These mutations confer the essential features of ion conduction in the cyclic nucleotide-gated ion channels; the mutant K+ channels display little selectivity among monovalent cations and are blocked by divalent cations. The property of K+ selectivity is related to the presence of two amino acids that are absent from the pore-forming region of the cyclic nucleotide-gated channels. These data demonstrate that very small differences in the primary structure of an ion channel can account for extreme functional diversity, and they suggest a possible connection between the pore-forming regions of K+, Ca2+, and cyclic nucleotide-gated ion channels.
D000595:Amino Acid Sequence; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002417:Cattle; D000242:Cyclic AMP / Q000494:pharmacology; D006152:Cyclic GMP / Q000494:pharmacology; D004330:Drosophila; D004553:Electric Conductivity; D015640:Ion Channel Gating / Q000187:drug effects; D007473:Ion Channels / Q000187:drug effects / Q000502:physiology*; D008274:Magnesium / Q000494:pharmacology; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009865:Oocytes / Q000502:physiology; D010944:Plants; D015221:Potassium Channels / Q000737:chemistry / Q000235:genetics* / Q000502:physiology*; D012160:Retina / Q000648:ultrastructure; D014162:Transfection; D014982:Xenopus laevis
D007473:Ion Channels; D015221:Potassium Channels; D000242:Cyclic AMP; D006152:Cyclic GMP; D008274:Magnesium; D002118:Calcium