首页> 外文期刊>The Journal of Physiology >The K+ channel signature sequence of murine Kir2.1: mutations that affect microscopic gating but not ionic selectivity.
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The K+ channel signature sequence of murine Kir2.1: mutations that affect microscopic gating but not ionic selectivity.

机译:鼠Kir2.1:突变的K +通道签名序列影响微观门控但不影响离子选择性。

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摘要

1. We have studied the effects on ionic selectivity and gating of Kir2.1 of replacing Tyr (Y) in the GYG signature sequence with Phe (Y145F), Leu (Y145L), Met (Y145M), Ala (Y145A) or Val (Y145V). 2. The mutant Y145F showed no changes in ionic selectivity (as indicated by the permeability coefficient ratios PNa/PK or PRb/PK), indicating that a hydrogen bond between Tyr and other residues is not essential for K+ selectivity. Y145L, Y145M, Y145A and Y145V did not express as monomers. 3. None of the channels made from covalently linked tandem dimers with wild-type and mutant subunits (WT-mutant) had altered ionic selectivity (PNa/PK or PRb/PK), indicating that 4-fold symmetry is not required. 4. Macroscopic currents activated under hyperpolarization and the time constants for activation were reduced e-fold per 23 mV hyperpolarization in wild-type. This gating, believed to be due to the release of polyamines from the pore, was little affected by mutation of Y14. There was similarly little effect on the relationship between chord conductance (gK) and membrane potential. 5. Unitary conductance (140 mM [K+]o) was also little affected by mutation and was reduced only in channels formed from WT-Y145M, from 22.7 +/- 0.4 pS (n = 5) in wild-type to 17.1 +/- 0.5 pS (n = 4) in WT-Y145M. 6. Steady-state recording of unitary currents showed that channel open times were affected by the residue that replaced Tyr in GYG. Channel openings were particularly brief in WT-Y145V, where the mean open time was reduced from 102 ms at -120 mV in wild-type to 6 ms in WT-Y145V. 7. Thus in Kir2.1, GFG can act as a K+ selectivity filter, as can G(L/M/A/V)G, at least in dimers also containing GYG. Channel open time duration depended on the residue at position 145, consistent with the H5 region helping to determine the dwell time of the channel in the open state.
机译:1.我们研究了用Phe(Y145F),Leu(Y145L),Met(Y145M),Ala(Y145A)或Val(替换GYG签名序列中的Tyr(Y)对Kir2.1的离子选择性和门控的影响。 Y145V)。 2.突变体Y145F的离子选择性没有变化(如渗透系数比PNa / PK或PRb / PK所示),表明Tyr和其他残基之间的氢键对于K +选择性不是必需的。 Y145L,Y145M,Y145A和Y145V不表示为单体。 3.由具有野生型和突变亚基(WT突变体)的共价连接的串联二聚体构成的通道均未改变离子选择性(PNa / PK或PRb / PK),表明不需要4倍对称性。 4.在野生型中,超极化下激活的宏观电流和激活的时间常数每23 mV超极化减少e倍。该门控被认为是由于多胺从孔中释放而引起的,几乎不受Y14突变的影响。类似地,对和弦电导(gK)与膜电位之间的关系影响很小。 5.单位电导(140 mM [K +] o)也几乎不受突变影响,仅在WT-Y145M形成的通道中降低,从野生型的22.7 +/- 0.4 pS(n = 5)降低到17.1 + / -在WT-Y145M中为0.5 pS(n = 4)。 6.单位电流的稳态记录表明,通道开放时间受到GYG中取代Tyr的残基的影响。通道开口在WT-Y145V中特别短暂,其平均打开时间从野生型的-120 mV的102 ms减少到WT-Y145V的6 ms。 7.因此,在Kir2.1中,至少在也包含GYG的二聚体中,GFG和G(L / M / A / V)G一样可以充当K +选择性过滤器。通道打开持续时间取决于位置145上的残基,与H5区域一致,有助于确定打开状态下通道的停留时间。

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