Role of surface electrostatics in the operation of a high-conductance Ca2+-activated K+ channel.
This paper demonstrates that local electric fields originating from negatively charged groups on a K+-specific ion channel modify its behavior. Single high-conductance, Ca2+-activated K+ channels were studied in neutral phospholipid bilayers. The channel protein surface charges were manipulated experimentally by carboxyl group esterification using trimethyloxonium (TMO) or by electrolyte screening. Three channel properties--ion conduction, ion blockade, and voltage-dependent gating--are affected by surface electrostatics. Negative charges increase the affinity of cationic pore blockers by establishing a local negative potential at the pore entrance; these charges modify channel gating by establishing a potential gradient across the ion channel; finally, both effects influence ion permeation through the pore.
MacKinnon
R
R
Howard Hughes Medical Institute, Brandeis University, Waltham, Massachusetts 02254.
Latorre
R
R
Miller
C
C
D002118:Calcium / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D004553:Electric Conductivity; D015640:Ion Channel Gating / Q000187:drug effects; D009132:Muscles / Q000378:metabolism; D015221:Potassium Channels / Q000187:drug effects*; D011189:Potassium Chloride / Q000494:pharmacology; D013499:Surface Properties
D015221:Potassium Channels; D011189:Potassium Chloride; D002118:Calcium