Abstract
The molecular mechanisms involved in slow C-type inactivation are not clear yet but may involve structural rearrangements in the outer pore domain paralleled by impaired K+ coordination in the selectivity filter (Choi et al., 1991; Hoshi et al., 1990; Lopez-Barneo et al., 1993). The mechanism of KCNQ1 inactivation and its modulation by external K+ are dissimilar to the mechanism described for C-type inactivation in Shaker-like K+ channels (Gibor et al., 2007). Further, inactivation of wild-type (WT) KCNQ1 channels becomes evident only in the characteristic hooked tail currents which reflect recovery from inactivation (Abitbol et al., 1999; Pusch et al., 1998; Tristani-Firouzi and Sanguinetti, 1998). We use a combination of functional-structural analysis combined with mathematical and 3D-structural modeling to gain insights into the structural rearrangements during KCNQ1-inactivation. We show that the Kv7.1 α-subunits act in a concerted way to initiate KCNQ1-inactivation.
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