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Allosteric voltage gating of potassium channels II. Mslo channel gating charge movement in the absence of Ca(2+).

Horrigan FT, Aldrich RW - J. Gen. Physiol. (1999)

Bottom Line: These results can be understood in terms of the allosteric voltage-gating scheme developed in the preceding paper (Horrigan, F.T., J.Physiol. 114:277-304).The model contains five open (O) and five closed (C) states arranged in parallel, and the kinetic and steady-state properties of mSlo gating currents exhibit multiple components associated with C-C, O-O, and C-O transitions.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular and Cellular Physiology, Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, California 94305, USA.

ABSTRACT
Large-conductance Ca(2+)-activated K(+) channels can be activated by membrane voltage in the absence of Ca(2+) binding, indicating that these channels contain an intrinsic voltage sensor. The properties of this voltage sensor and its relationship to channel activation were examined by studying gating charge movement from mSlo Ca(2+)-activated K(+) channels in the virtual absence of Ca(2+) (<1 nM). Charge movement was measured in response to voltage steps or sinusoidal voltage commands. The charge-voltage relationship (Q-V) is shallower and shifted to more negative voltages than the voltage-dependent open probability (G-V). Both ON and OFF gating currents evoked by brief (0.5-ms) voltage pulses appear to decay rapidly (tau(ON) = 60 microseconds at +200 mV, tau(OFF) = 16 microseconds at -80 mV). However, Q(OFF) increases slowly with pulse duration, indicating that a large fraction of ON charge develops with a time course comparable to that of I(K) activation. The slow onset of this gating charge prevents its detection as a component of I(gON), although it represents approximately 40% of the total charge moved at +140 mV. The decay of I(gOFF) is slowed after depolarizations that open mSlo channels. Yet, the majority of open channel charge relaxation is too rapid to be limited by channel closing. These results can be understood in terms of the allosteric voltage-gating scheme developed in the preceding paper (Horrigan, F.T., J. Cui, and R.W. Aldrich. 1999. J. Gen. Physiol. 114:277-304). The model contains five open (O) and five closed (C) states arranged in parallel, and the kinetic and steady-state properties of mSlo gating currents exhibit multiple components associated with C-C, O-O, and C-O transitions.

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Mentions: This diagram illustrates the idea that mSlo channels undergo a transition between a closed (C) and open (O) conformation, and that this transition is influenced allosterically by the state of four independent and identical voltage sensors (one for each subunit). We assume each voltage sensor can undergo a transition between a resting (R) and an activated (A) conformation, and the equilibrium constant for the C–O transition (L) increases by a constant factor (D) for each voltage sensor that is activated. Similarly, the equilibrium constant for voltage sensor activation (J) increases D-fold in favor of the activated state, when the channel opens. Therefore, the factor D embodies the allosteric interaction between voltage-sensor activation and channel opening. This mechanism results in a gating scheme (Fig. 1) that contains a parallel arrangement of open and closed states.


Allosteric voltage gating of potassium channels II. Mslo channel gating charge movement in the absence of Ca(2+).

Horrigan FT, Aldrich RW - J. Gen. Physiol. (1999)

© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2230644&req=5

Mentions: This diagram illustrates the idea that mSlo channels undergo a transition between a closed (C) and open (O) conformation, and that this transition is influenced allosterically by the state of four independent and identical voltage sensors (one for each subunit). We assume each voltage sensor can undergo a transition between a resting (R) and an activated (A) conformation, and the equilibrium constant for the C–O transition (L) increases by a constant factor (D) for each voltage sensor that is activated. Similarly, the equilibrium constant for voltage sensor activation (J) increases D-fold in favor of the activated state, when the channel opens. Therefore, the factor D embodies the allosteric interaction between voltage-sensor activation and channel opening. This mechanism results in a gating scheme (Fig. 1) that contains a parallel arrangement of open and closed states.

Bottom Line: These results can be understood in terms of the allosteric voltage-gating scheme developed in the preceding paper (Horrigan, F.T., J.Physiol. 114:277-304).The model contains five open (O) and five closed (C) states arranged in parallel, and the kinetic and steady-state properties of mSlo gating currents exhibit multiple components associated with C-C, O-O, and C-O transitions.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular and Cellular Physiology, Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, California 94305, USA.

ABSTRACT
Large-conductance Ca(2+)-activated K(+) channels can be activated by membrane voltage in the absence of Ca(2+) binding, indicating that these channels contain an intrinsic voltage sensor. The properties of this voltage sensor and its relationship to channel activation were examined by studying gating charge movement from mSlo Ca(2+)-activated K(+) channels in the virtual absence of Ca(2+) (<1 nM). Charge movement was measured in response to voltage steps or sinusoidal voltage commands. The charge-voltage relationship (Q-V) is shallower and shifted to more negative voltages than the voltage-dependent open probability (G-V). Both ON and OFF gating currents evoked by brief (0.5-ms) voltage pulses appear to decay rapidly (tau(ON) = 60 microseconds at +200 mV, tau(OFF) = 16 microseconds at -80 mV). However, Q(OFF) increases slowly with pulse duration, indicating that a large fraction of ON charge develops with a time course comparable to that of I(K) activation. The slow onset of this gating charge prevents its detection as a component of I(gON), although it represents approximately 40% of the total charge moved at +140 mV. The decay of I(gOFF) is slowed after depolarizations that open mSlo channels. Yet, the majority of open channel charge relaxation is too rapid to be limited by channel closing. These results can be understood in terms of the allosteric voltage-gating scheme developed in the preceding paper (Horrigan, F.T., J. Cui, and R.W. Aldrich. 1999. J. Gen. Physiol. 114:277-304). The model contains five open (O) and five closed (C) states arranged in parallel, and the kinetic and steady-state properties of mSlo gating currents exhibit multiple components associated with C-C, O-O, and C-O transitions.

Show MeSH
Related in: MedlinePlus