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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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Ig Simulations using modified parameters. (A) Ig evoked at +140 mV in response to pulses of different duration (HP = −100 mV) are plotted on two different time scales and compared with the predictions of the allosteric scheme using modified parameters corresponding to Case B in Fig. 10 (solid lines, Table : Case B). (B) Ig evoked at +224 mV is also fit by the model. (C) QOFF–Qss corresponding to the records in A are plotted on a semilog scale, demonstrating that the model reproduces all three components of QOFF. (D) Qp(t) from Fig. 6 B is reproduced by the model (QON(t)) for V ≥ +140 mV but the slow component amplitude is underestimated at lower voltages. (E) The Cg–V relationship measured from the same patch as in A at 868 Hz is compared with simulations of the allosteric scheme corresponding to Case A and Case B parameters (solid lines). Dashed lines indicate the derivatives of the Qc–V and Qo–V relationships (Q ′C, Q ′O). The scale bar represents 50 fF.
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Figure 11: Ig Simulations using modified parameters. (A) Ig evoked at +140 mV in response to pulses of different duration (HP = −100 mV) are plotted on two different time scales and compared with the predictions of the allosteric scheme using modified parameters corresponding to Case B in Fig. 10 (solid lines, Table : Case B). (B) Ig evoked at +224 mV is also fit by the model. (C) QOFF–Qss corresponding to the records in A are plotted on a semilog scale, demonstrating that the model reproduces all three components of QOFF. (D) Qp(t) from Fig. 6 B is reproduced by the model (QON(t)) for V ≥ +140 mV but the slow component amplitude is underestimated at lower voltages. (E) The Cg–V relationship measured from the same patch as in A at 868 Hz is compared with simulations of the allosteric scheme corresponding to Case A and Case B parameters (solid lines). Dashed lines indicate the derivatives of the Qc–V and Qo–V relationships (Q ′C, Q ′O). The scale bar represents 50 fF.

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)

Ig Simulations using modified parameters. (A) Ig evoked at +140 mV in response to pulses of different duration (HP = −100 mV) are plotted on two different time scales and compared with the predictions of the allosteric scheme using modified parameters corresponding to Case B in Fig. 10 (solid lines, Table : Case B). (B) Ig evoked at +224 mV is also fit by the model. (C) QOFF–Qss corresponding to the records in A are plotted on a semilog scale, demonstrating that the model reproduces all three components of QOFF. (D) Qp(t) from Fig. 6 B is reproduced by the model (QON(t)) for V ≥ +140 mV but the slow component amplitude is underestimated at lower voltages. (E) The Cg–V relationship measured from the same patch as in A at 868 Hz is compared with simulations of the allosteric scheme corresponding to Case A and Case B parameters (solid lines). Dashed lines indicate the derivatives of the Qc–V and Qo–V relationships (Q ′C, Q ′O). The scale bar represents 50 fF.
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getmorefigures.php?uid=PMC2230644&req=5

Figure 11: Ig Simulations using modified parameters. (A) Ig evoked at +140 mV in response to pulses of different duration (HP = −100 mV) are plotted on two different time scales and compared with the predictions of the allosteric scheme using modified parameters corresponding to Case B in Fig. 10 (solid lines, Table : Case B). (B) Ig evoked at +224 mV is also fit by the model. (C) QOFF–Qss corresponding to the records in A are plotted on a semilog scale, demonstrating that the model reproduces all three components of QOFF. (D) Qp(t) from Fig. 6 B is reproduced by the model (QON(t)) for V ≥ +140 mV but the slow component amplitude is underestimated at lower voltages. (E) The Cg–V relationship measured from the same patch as in A at 868 Hz is compared with simulations of the allosteric scheme corresponding to Case A and Case B parameters (solid lines). Dashed lines indicate the derivatives of the Qc–V and Qo–V relationships (Q ′C, Q ′O). The scale bar represents 50 fF.
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