Richard W. Aldrich

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Voltage-dependent gating behavior of Shaker potassium channels without N-type inactivation (ShB delta 6-46) expressed in Xenopus oocytes was studied. The voltage dependence of the steady-state open probability indicated that the activation process involves the movement of the equivalent of 12-16 electronic charges across the membrane. The sigmoidal kinetics(More)
The potassium channels encoded by the Drosophila Shaker gene activate and inactivate rapidly when the membrane potential becomes more positive. Site-directed mutagenesis and single-channel patch-clamp recording were used to explore the molecular transitions that underlie inactivation in Shaker potassium channels expressed in Xenopus oocytes. A region near(More)
Predictions of different classes of gating models involving identical conformational changes in each of four subunits were compared to the gating behavior of Shaker potassium channels without N-type inactivation. Each model was tested to see if it could simulate the voltage dependence of the steady state open probability, and the kinetics of the(More)
After removal of N-type inactivation in Shaker K channels another inactivation process remains (C-type inactivation). The C-type inactivation time course is reversibly slowed when external [K+] increases. The effect of K+ is mimicked by Rb+ and, with less potency, by the less permeant ions Na+, Cs+, and NH4+. These results, which can be explained by the(More)
The kinetic and steady-state properties of macroscopic mslo Ca-activated K 1 currents were studied in excised patches from Xenopus oocytes. In response to voltage steps, the timecourse of both activation and deactivation, but for a brief delay in activation, could be approximated by a single exponential function over a wide range of voltages and internal Ca(More)
To determine how intracellular Ca 2 ! and membrane voltage regulate the gating of large conductance Ca 2 ! -activated K ! (BK) channels, we examined the steady-state and kinetic properties of mSlo1 ionic and gating currents in the presence and absence of Ca 2 ! over a wide range of voltage. The activation of unliganded mSlo1 channels can be accounted for by(More)
Shaker potassium channels inactivate and recover from inactivation with multiple exponential components, suggesting the presence of multiple inactivation processes. We describe two different types of inactivation in Shaker potassium channels. N-type inactivation can occur as rapidly as a few milliseconds and has been shown to involve an intracellular region(More)
Activation of large conductance Ca(2+)-activated K(+) channels is controlled by both cytoplasmic Ca(2+) and membrane potential. To study the mechanism of voltage-dependent gating, we examined mSlo Ca(2+)-activated K(+) currents in excised macropatches from Xenopus oocytes in the virtual absence of Ca(2+) (<1 nM). In response to a voltage step, I(K)(More)
It has long been argued that algorithms that find correlated mutations in multiple sequence alignments can be used to find structurally or functionally important residues in proteins. We examined the properties of four different methods for detecting these correlated mutations. On both simple, artificial alignments and real alignments from the Pfam(More)