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Distinct potassium channel types in brain capillary pericytes
Biophysical Journal ( IF 3.4 ) Pub Date : 2024-03-05 , DOI: 10.1016/j.bpj.2024.03.004
Maria Sancho , Nicholas R. Klug , Osama F. Harraz , David Hill-Eubanks , Mark T. Nelson

Capillaries, composed of electrically coupled endothelial cells and overlying pericytes, constitute the vast majority of blood vessels in the brain. The most arteriole-proximate three to four branches of the capillary bed are covered by -actin-expressing, contractile pericytes. These mural cells have a distinctive morphology and express different markers compared with their smooth muscle cell (SMC) cousins but share similar excitation-coupling contraction machinery. Despite this similarity, pericytes are considerably more depolarized than SMCs at low intravascular pressures. We have recently shown that pericytes, such as SMCs, possess functional voltage-dependent Ca channels and ATP-sensitive K channels. Here, we further investigate the complement of pericyte ion channels, focusing on members of the K channel superfamily. Using NG2-DsRed-transgenic mice and diverse configurations of the patch-clamp technique, we demonstrate that pericytes display robust inward-rectifier K currents that are primarily mediated by the Kir2 family, based on their unique biophysical characteristics and sensitivity to micromolar concentrations of Ba. Moreover, multiple lines of evidence, including characteristic kinetics, sensitivity to specific blockers, biophysical attributes, and distinctive single-channel properties, established the functional expression of two voltage-dependent K channels: K1 and BK. Although these three types of channels are also present in SMCs, they exhibit distinctive current density and kinetics profiles in pericytes. Collectively, these findings underscore differences in the operation of shared molecular features between pericytes and SMCs and highlight the potential contribution of these three K ion channels in setting pericyte membrane potential, modulating capillary hemodynamics, and regulating cerebral blood flow.

中文翻译:

脑毛细血管周细胞中不同的钾通道类型

毛细血管由电耦合的内皮细胞和覆盖的周细胞组成,构成了大脑中的绝大多数血管。最靠近小动脉的毛细血管床的三到四个分支被表达β肌动蛋白的收缩周细胞覆盖。与平滑肌细胞 (SMC) 近亲相比,这些壁细胞具有独特的形态并表达不同的标记,但具有相似的激发耦合收缩机制。尽管存在这种相似性,但在低血管内压下,周细胞比 SMC 去极化程度要高得多。我们最近表明,周细胞(例如 SMC)具有功能性电压依赖性 Ca 通道和 ATP 敏感 K 通道。在这里,我们进一步研究了周细胞离子通道的补充,重点关注 K 通道超家族的成员。使用 NG2-DsRed 转基因小鼠和不同配置的膜片钳技术,我们证明周细胞显示出强大的内向整流 K 电流,该电流主要由 Kir2 家族介导,基于其独特的生物物理特征和对微摩尔浓度 Ba 的敏感性。此外,多种证据,包括特征动力学、对特定阻断剂的敏感性、生物物理属性和独特的单通道特性,确定了两个电压依赖性 K 通道:K1 和 BK 的功能表达。尽管这三种类型的通道也存在于 SMC 中,但它们在周细胞中表现出独特的电流密度和动力学特征。总的来说,这些发现强调了周细胞和 SMC 之间共有分子特征的运作差异,并强调了这三个 K 离子通道在设置周细胞膜电位、调节毛细血管血流动力学和调节脑血流方面的潜在贡献。
更新日期:2024-03-05
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