Characterization of the Driving Force as a Modulator of Gating in Cardiac ATP-sensitive K+ Channels — Evidence for Specific Elementary Properties
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Single cardiac ATP-sensitive K+ channels and, comparatively, two other members of the inwardly rectifying K+ channel family, cardiac K+ (ir) and K+ (ACh) channels, were studied in the inside-out recording mode in order to analyze influence and significance of the electrochemical K+ gradient for open-state kinetics of these K+ channels.
The conductive state of K+ (ATP) channels was defined as a function of the electrochemical K+ gradient in that increased driving force correlates with shortened open-channel lifetime. Flux coupling of gating can be largely excluded as the underlying mechanism for two reasons: (i) τopen proved identical in 23 pS, 56 pS and 80 pS channels; (ii) K+ (ATP) channel protonation by an external pH shift from 9.5 to 5.5 reduced conductance without a concomitant detectable change of τopen. Since gating continued to operate at E K , i.e., in the absence of K+ permeation through the pore, K+ driving force cannot be causally involved in gating. Rather the driving force acts to modulate the gating process similar to Rb+ whose interference with an externally located binding site stabilizes the open state. In K+ (ir) and K+ (ACh) channels, the open state is essentially independent on driving force meaning that their gating apparatus does not sense the electrochemical K+ gradient. Thus, K+ (ATP) channels differ in an important functional aspect which may be tentatively explained by a structural peculiarity of their gating apparatus.
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