Conformational changes associated with ion permeation in L-type calcium channels.
The mechanism by which ions deliver their message to effector proteins involves a change in the protein conformation which is induced by the specific interaction of the ion with its binding site on the protein. In the case of an ion-channel protein, conformational changes induced by permeant ions and the consequences for channel function have received little attention. Here we report that binding of permeant cations to an intra-channel binding site of the dihydropyridine (DHP)-sensitive (L-type) Ca2+ channel leads to a conformational change which destabilizes the protonated state of a group on the external channel surface, and can shift its apparent pK value by more than 2 pH units. The lifetime of the protonated state correlates with the occupancy of an intra-channel binding site by the permeant cation. The demonstration of such conformational changes in a channel protein induced by the permeant ion has important implications for realistic models of the mechanism of ion permeation.
D000818:Animals; D030161:Avian Proteins; D002118:Calcium / Q000378:metabolism*; D002414:Cations, Monovalent; D002460:Cell Line; D004095:Dihydropyridines / Q000494:pharmacology; D006168:Guinea Pigs; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D008565:Membrane Proteins / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism; D011487:Protein Conformation
D030161:Avian Proteins; C051235:CCC protein, chicken; D002414:Cations, Monovalent; D004095:Dihydropyridines; D007473:Ion Channels; D008565:Membrane Proteins; C038806:1,4-dihydropyridine; D002118:Calcium