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Biophys J, February 2000, p. 761-772, Vol. 78, No. 2
Department of Molecular and Cellular Physiology, Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, California 94305 USA
The study and characterization of unliganded openings is
of central significance for the elucidation of gating mechanisms for
allosteric ligand-gated ion channels. Unliganded openings have been
reported for many channel types, but their low open probability can
make it difficult to study their kinetics in detail. Because the large
conductance calcium-activated potassium channel mSlo is
sensitive to both intracellular calcium and to membrane potential, we
have been able to obtain stable unliganded single-channel recordings of
mSlo with relatively high opening probability. We have
found that the single-channel gating behavior of mSlo is complex, with multiple open and closed states, even when no ligand is
present. Our results rule out a Monod-Wyman-Changeux allosteric mechanism with a central voltage-dependent concerted step, and they
support the existence of quaternary states with less than the full
number of voltage sensors activated, as has been suggested by previous
work involving measurements of gating currents.
Biophys J, February 2000, p. 761-772, Vol. 78, No. 2
© 2000 by the Biophysical Society 0006-3495/00/02/761/12 $2.00
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