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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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Simulations of Fast Ig. (A) A family of IgON evoked at different voltages (0 to +140 mV) is compared with the prediction of the allosteric scheme (solid lines). Data and simulated traces were both evoked in response to filtered voltage pulses (20 kHz) and then filtered at 20 kHz. (B) A family of gating currents evoked at +140 mV in response to pulses of different duration (from Fig. 5 A) is fit by the allosteric model (solid lines). Model parameters for panels A and B are as shown in Table  (Case A) with the exception that α and β were decreased by 2% (α(0) = 1,080 s−1, β(0) = 31,681 s−1) to match this experiment. (C) τgFast measured from simulated traces at different voltages is plotted versus voltage (filled circles) and compared with the τF–V relationship predicted from the parameters assigned to the R–A transition in the model (solid line, τ = 1/(α+β); Case A in Table ). Open symbols indicate the time constant of the Medium OFF component (τM) measured from several patches. Lines through these data represent predictions of the allosteric scheme (see text). (D) The Qfast–V relationship measured from simulated currents (symbols) is compared with the QC–V relationship specified by the model (line). (E) The time course of Qp predicted by the allosteric model (lines) accounts for the fast component of ON charge but underestimates the magnitude of the slow component.
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Figure 9: Simulations of Fast Ig. (A) A family of IgON evoked at different voltages (0 to +140 mV) is compared with the prediction of the allosteric scheme (solid lines). Data and simulated traces were both evoked in response to filtered voltage pulses (20 kHz) and then filtered at 20 kHz. (B) A family of gating currents evoked at +140 mV in response to pulses of different duration (from Fig. 5 A) is fit by the allosteric model (solid lines). Model parameters for panels A and B are as shown in Table (Case A) with the exception that α and β were decreased by 2% (α(0) = 1,080 s−1, β(0) = 31,681 s−1) to match this experiment. (C) τgFast measured from simulated traces at different voltages is plotted versus voltage (filled circles) and compared with the τF–V relationship predicted from the parameters assigned to the R–A transition in the model (solid line, τ = 1/(α+β); Case A in Table ). Open symbols indicate the time constant of the Medium OFF component (τM) measured from several patches. Lines through these data represent predictions of the allosteric scheme (see text). (D) The Qfast–V relationship measured from simulated currents (symbols) is compared with the QC–V relationship specified by the model (line). (E) The time course of Qp predicted by the allosteric model (lines) accounts for the fast component of ON charge but underestimates the magnitude of the slow component.

Mentions: The results discussed thus far are qualitatively consistent with the behavior of the allosteric gating scheme (Fig. 1). Simulations based on the model as shown in Fig. 9, Fig. 10, and Fig. 11 also reproduce the major features of the data. However, the parameters that were ultimately used to fit Ig differ from those used to describe ionic currents (Horrigan et al. 1999). Some of these differences are small and may simply reflect a greater accuracy in characterizing fast voltage-sensor movement with gating currents. Other differences, relating to the slow charge movement, suggest that ionic conditions alter mSlo channel gating.


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)

Simulations of Fast Ig. (A) A family of IgON evoked at different voltages (0 to +140 mV) is compared with the prediction of the allosteric scheme (solid lines). Data and simulated traces were both evoked in response to filtered voltage pulses (20 kHz) and then filtered at 20 kHz. (B) A family of gating currents evoked at +140 mV in response to pulses of different duration (from Fig. 5 A) is fit by the allosteric model (solid lines). Model parameters for panels A and B are as shown in Table  (Case A) with the exception that α and β were decreased by 2% (α(0) = 1,080 s−1, β(0) = 31,681 s−1) to match this experiment. (C) τgFast measured from simulated traces at different voltages is plotted versus voltage (filled circles) and compared with the τF–V relationship predicted from the parameters assigned to the R–A transition in the model (solid line, τ = 1/(α+β); Case A in Table ). Open symbols indicate the time constant of the Medium OFF component (τM) measured from several patches. Lines through these data represent predictions of the allosteric scheme (see text). (D) The Qfast–V relationship measured from simulated currents (symbols) is compared with the QC–V relationship specified by the model (line). (E) The time course of Qp predicted by the allosteric model (lines) accounts for the fast component of ON charge but underestimates the magnitude of the slow component.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2230644&req=5

Figure 9: Simulations of Fast Ig. (A) A family of IgON evoked at different voltages (0 to +140 mV) is compared with the prediction of the allosteric scheme (solid lines). Data and simulated traces were both evoked in response to filtered voltage pulses (20 kHz) and then filtered at 20 kHz. (B) A family of gating currents evoked at +140 mV in response to pulses of different duration (from Fig. 5 A) is fit by the allosteric model (solid lines). Model parameters for panels A and B are as shown in Table (Case A) with the exception that α and β were decreased by 2% (α(0) = 1,080 s−1, β(0) = 31,681 s−1) to match this experiment. (C) τgFast measured from simulated traces at different voltages is plotted versus voltage (filled circles) and compared with the τF–V relationship predicted from the parameters assigned to the R–A transition in the model (solid line, τ = 1/(α+β); Case A in Table ). Open symbols indicate the time constant of the Medium OFF component (τM) measured from several patches. Lines through these data represent predictions of the allosteric scheme (see text). (D) The Qfast–V relationship measured from simulated currents (symbols) is compared with the QC–V relationship specified by the model (line). (E) The time course of Qp predicted by the allosteric model (lines) accounts for the fast component of ON charge but underestimates the magnitude of the slow component.
Mentions: The results discussed thus far are qualitatively consistent with the behavior of the allosteric gating scheme (Fig. 1). Simulations based on the model as shown in Fig. 9, Fig. 10, and Fig. 11 also reproduce the major features of the data. However, the parameters that were ultimately used to fit Ig differ from those used to describe ionic currents (Horrigan et al. 1999). Some of these differences are small and may simply reflect a greater accuracy in characterizing fast voltage-sensor movement with gating currents. Other differences, relating to the slow charge movement, suggest that ionic conditions alter mSlo channel gating.

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