H+ ion modulation of C-type inactivation of Shaker K+ channels.
The participation of an extracellular loop in C-type inactivation of voltage-gated K+ channels was investigated. A wild-type phenylalanine (at position 425) between the fifth putative transmembrane segment (S5) and the pore region of the Shaker K+ channel was mutated to a histidine and the functional consequences of protonating the imidizole group of the histidine were examined. C-type inactivation of both wild-type and mutant channels was sensitive to external pH over the range of 5.2-8. The pH dependence of wild-type channels was characterized by an apparent pK value of 5. 0. The inactivation kinetics of F425H mutant channels had a pH dependence with a pK of 5.8 - in addition to the pH dependence of the wild-type channels. Moreover, at pH 7 and 8 the voltage dependence of C-type inactivation kinetics was manifest only in the F425H mutant channels. C-type inactivation in wild-type channels involves a chemical group with a low pK. Taken together, these results suggest that residues located in the extracellular S5-pore loop of the Shaker K+ channel participate in C-type inactivation.
Pérez-Cornejo
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University of Rochester, School of Medicine and Dentistry, 601 Elmwood Avenue, Box 711, Rochester, NY 14642-8642, USA. gperez@deimos.tc.uaslp.mx
D000818:Animals; D001001:Anura; D004553:Electric Conductivity; D005260:Female; D018014:Gene Transfer Techniques; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008433:Mathematics; D016296:Mutagenesis; D009865:Oocytes / Q000378:metabolism; D016133:Polymerase Chain Reaction; D015221:Potassium Channels / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D011522:Protons; D051637:Shaker Superfamily of Potassium Channels; D013329:Structure-Activity Relationship
D015221:Potassium Channels; D011522:Protons; D051637:Shaker Superfamily of Potassium Channels