The HVCN1 voltage-gated proton channel contributes to pH regulation in canine ventricular myocytes.
The HVCN1 voltage-gated proton channel contributes to pH regulation in canine ventricular myocytes.
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DOI：
10.1113/jp282126
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发表时间：
2022-05
影响因子：
5.5
通讯作者：
Wang, Hong-Sheng
中科院分区：
文献类型：
--
作者：
Ma, Jianyong;Gao, Xiaoqian;Li, Yutian;DeCoursey, Thomas E.;Shull, Gary E.;Wang, Hong-Sheng
心肌细胞内 pH 值 (pHi) 的调节对于心脏功能至关重要；然而，目前已知的从心肌细胞直接或间接挤出酸的机制似乎不足以有效地挤出体内条件下产生的大量H+负荷。在心肌细胞中，由 HVCN1 质子通道介导的电压敏感 H+ 通道活性将是处理 H+ 的高效方法，同时避免 Na+ 负载，如通过 Na+/H+ 交换直接酸挤出或通过 Na+-HCO3− 共转运间接酸挤出期间发生的情况。 PCR和免疫印迹显示犬心脏中HVCN1 mRNA和蛋白的表达。犬心室肌细胞的膜片钳分析揭示了具有高度 H+ 选择性的电压门控 H+ 电流。电流被外部 Zn2+ 和 HVCN1 阻断剂 5-氯-2-胍基苯并咪唑 (ClGBI) 阻断。电流的门控和 Zn2+ 阻断都受到跨膜 pH 梯度的强烈影响。观察到的电流的所有特征均与 HVCN1 介导的 H+ 电流的已知特征一致。单独或联合抑制 HVCN1 和 NHE1 Na+/H+ 交换剂表明，任一机制在很大程度上足以维持跳动心肌细胞的 pHi，但抑制这两种活性会导致快速酸化。这些结果表明，HVCN1 在犬心室肌细胞中表达，并提供主要的 H+ 挤出活性，其能力与 NHE1 相似。在体内跳动的心脏中，这种活性将允许在每个动作电位期间不依赖于 Na+ 挤出 H+，并且当与阴离子转运机制功能性耦合时，可以促进转运介导的 CO2 处理。 HVCN1 质子通道在犬心室肌细胞中表达，有助于 H+ 排出。
Regulation of intracellular pH (pHi) in cardiomyocytes is crucial for cardiac function; however, currently known mechanisms for direct or indirect extrusion of acid from cardiomyocytes seem insufficient for energetically-efficient extrusion of the massive H+ loads generated under in vivo conditions. In cardiomyocytes, voltage-sensitive H+ channel activity mediated by the HVCN1 proton channel would be a highly efficient means of disposing of H+, while avoiding Na+-loading, as occurs during direct acid extrusion via Na+/H+ exchange or indirect acid extrusion via Na+-HCO3− cotransport. PCR and immunoblotting demonstrated expression of HVCN1 mRNA and protein in canine heart. Patch clamp analysis of canine ventricular myocytes revealed a voltage-gated H+ current that was highly H+-selective. The current was blocked by external Zn2+ and the HVCN1 blocker 5-chloro-2-guanidinobenzimidazole (ClGBI). Both the gating and Zn2+ blockade of the current were strongly influenced by the pH gradient across the membrane. All characteristics of the observed current were consistent with the known hallmarks of HVCN1-mediated H+ current. Inhibition of HVCN1 and the NHE1 Na+/H+ exchanger, singly and in combination, showed that either mechanism is largely sufficient to maintain pHi in beating cardiomyocytes, but that inhibition of both activities causes rapid acidification. These results show that HVCN1 is expressed in canine ventricular myocytes and provides a major H+-extrusion activity, with a capacity similar to that of NHE1. In the beating heart in vivo, this activity would allow Na+-independent extrusion of H+ during each action potential and, when functionally coupled with anion transport mechanisms, could facilitate transport-mediated CO2 disposal. The HVCN1 proton channel is expressed in canine ventricular myocytes and contributes to H+ extrusion.
DOI：
10.1016/j.pbiomolbio.2012.07.010
发表时间：
2012-10
影响因子：
3.8
作者：
McNary TG;Spitzer KW;Holloway H;Bridge JH;Kohl P;Sachse FB
通讯作者：
Sachse FB
AE3氯化物/碳酸氢盐交换器缺乏引起的失明。
影响因子：
3.7
作者：
Alvarez, Bernardo V.;Gilmour, Gregory S.;Mema, Silvina C.;Martin, Brent T.;Shull, Gary E.;Casey, Joseph R.;Sauve, Yves
通讯作者：
Sauve, Yves