Characterization of the driving force as a modulator of gating in cardiac ATP-sensitive K+ channels - evidence for specific elementary properties.
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) tauopen 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 tauopen. Since gating continued to operate at EK, 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.
Physiological Institute of the University, Hermann-Herder-Str. 7, D-79104 Freiburg/Br., Germany.
I
I
Benz
K
K
Haverkampf
M
M
Kohlhardt
D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D004553:Electric Conductivity; D004563:Electrochemistry; D006321:Heart / Q000502:physiology*; D006325:Heart Atria; D006352:Heart Ventricles; D006863:Hydrogen-Ion Concentration; D015640:Ion Channel Gating; D007700:Kinetics; D008564:Membrane Potentials; D009206:Myocardium / Q000166:cytology; D015221:Potassium Channels / Q000502:physiology*; D051381:Rats; D012044:Regression Analysis
D015221:Potassium Channels