Differential pH sensitivity of Kir4.1 and Kir4.2 potassium channels and their modulation by heteropolymerisation with Kir5.1
Differential pH sensitivity of Kir4.1 and Kir4.2 potassium channels and their modulation by heteropolymerisation with Kir5.1
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DOI：
10.1111/j.1469-7793.2001.0359f.x
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发表时间：
2001-04-15
影响因子：
5.5
通讯作者：
Tucker, SJ
中科院分区：
文献类型：
--
作者：
Pessia, M;Imbrici, P;Tucker, SJ
1. 内向整流钾通道 Kir5.1 似乎仅通过与 Kir4.1 或 Kir4.2 共表达才能形成功能通道。 Kir4.1-Kir5.1 异聚通道已被证明存在于体内肾小管上皮中。然而，Kir5.1 在许多其他未发现 Kir4.1 的组织中表达。使用 Kir5.1 特异性抗体，我们将 Kir5.1 表达定位在胰腺中，而在该组织中，Kir4.2 也高度表达。2．异聚 Kir5.1-Kir4.1 通道对细胞内酸化的敏感性明显高于 Kir4.1 电流。我们证明这种敏感性的增加主要是由于 Kir5.1.3 对 Kir4.1 内在 pH 敏感性的调节。研究发现，由于涉及 C 末端的额外 pH 感应机制，Kir4.2 的 pH 敏感性 (pK(a) = 7.1) 明显高于 Kir4.1 (pK(a7) = 5.99)。结果是，与 Kir5.1 共表达不会导致异聚体 Kir4.2-Kir5.1 通道的 pH 敏感性发生重大变化。4。 Kir4.2 的细胞附着单通道分析揭示了一个具有高开放概率 (P-o > 0.9) 的通道和类似于 25 pS 的单通道电导，而与 Kir5.1 的共表达产生了新的突发通道 (P-o < 0.3) 和类似于 54 pS 的主电导，并具有多种亚电导状态。 5。这些结果表明，在 Kir4.1 不表达的组织（例如胰腺）中，Kir5.1 可能与 Kir4.2 形成异聚通道，并且这些新通道可能受到细胞内 pH 值变化的调节。此外，Kir4.2 的极端 pH 敏感性对该亚基作为同源四聚体通道的作用具有影响。
1. The inwardly rectifying potassium channel Kir5.1 appears to form functional channels only by coexpression with either Kir4.1 or Kir4.2. Kir4.1-Kir5.1 heteromeric channels have been shown to exist in vivo in renal tubular epithelia. However, Kir5.1 is expressed in many other tissues where Kir4.1 is not found. Using Kir5.1-specific antibodies we have localised Kir5.1 expression in the pancreas, a tissue where Kir4.2 is also highly expressed.2. Heteromeric Kir5.1-Kir4.1 channels are significantly more sensitive to intracellular acidification than Kir4.1 currents. We demonstrate that this increased sensitivity is primarily due to modulation of the intrinsic Kir4.1 pH sensitivity by Kir5.1.3. Kir4.2 was found to be significantly more pH sensitive (pK(a) = 7.1) than Kir4.1 (pK(a7) = 5.99) due to an additional pH-sensing mechanism involving the C-terminus. Bs a result, coexpression with Kir5.1 does not cause a major shift in the pH sensitivity of the heteromeric Kir4.2-Kir5.1 channel.4. Cell-attached single channel analysis of Kir4.2 revealed a channel with a high open probability (P-o > 0.9) and single channel conductance of similar to 25 pS, whilst coexpression with Kir5.1 produced novel bursting channels (P-o < 0.3) and a principal conductance of similar to 54 pS with several subconductance states.5. These results indicate that Kir5.1 may form heteromeric channels with Kir4.2 in tissues where Kir4.1 is not expressed (e.g. pancreas) and that these novel channels are likely to be regulated by changes in intracellular pH. In addition, the extreme pH sensitivity of Kir4.2 has implications for the role of this subunit as a homotetrameric channel.