Voltage-gated Kv7 (or KCNQ) channels control activity of excitable cells, including vascular smooth muscle cells (VSMCs), by setting their resting membrane potential and controlling other excitability parameters. Excitation-contraction coupling in muscle cells is mediated by Ca²⁺ but until now, the exact role of Kv7 channels in cytosolic Ca²⁺ dynamics in VSMCs has not been fully elucidated. We utilised microfluorimetry to investigate the impact of Kv7 channel activity on intracellular Ca²⁺ levels and electrical activity of rat A7r5 VSMCs and primary human internal mammary artery (IMA) SMCs. Both, direct (XE991) and G protein coupled receptor mediated (vasopressin, AVP) Kv7 channel inhibition induced robust Ca²⁺ oscillations, which were significantly reduced in the presence of Kv7 channel activator, retigabine, L-type Ca²⁺ channel inhibitor, nifedipine, or T-type Ca²⁺ channel inhibitor, NNC 55-0396, in A7r5 cells. Membrane potential measured using FluoVolt exhibited a slow depolarisation followed by a burst of sharp spikes in response to XE991; spikes were temporally correlated with Ca²⁺ oscillations. Phospholipase C inhibitor (edelfosine) reduced AVP-induced, but not XE991-induced Ca²⁺ oscillations. AVP and XE991 induced a large increase of [Ca²⁺]_i in human IMA, which was also attenuated with retigabine, nifedipine and NNC 55-0396. RT-PCR, immunohistochemistry and electrophysiology suggested that Kv7.5 was the predominant Kv7 subunit in both rat and human arterial SMCs; CACNA1C (Cav1.2; L-type) and CACNA1 G (Cav3.1; T-type) were the most abundant voltage-gated Ca²⁺ channel gene transcripts in both types of VSMCs. This study establishes Kv7 channels as key regulators of Ca²⁺ signalling in VSMCs with Kv7.5 playing a dominant role.

电压门控 Kv7（或 KCNQ）通道通过设置静息膜电位并控制其他兴奋性参数来控制可兴奋细胞（包括血管平滑肌细胞 (VSMC)）的活动。肌肉细胞中的兴奋-收缩耦合是由 Ca ²⁺介导的，但迄今为止，Kv7 通道在 VSMC 胞质 Ca ²⁺动力学中的确切作用尚未完全阐明。我们利用微荧光测定法研究 Kv7 通道活性对大鼠 A7r5 VSMC 和原代人乳内动脉 (IMA) SMC 的细胞内 Ca ^{2+水平和电活动的影响。}直接 (XE991) 和 G 蛋白偶联受体介导的 (加压素、AVP) Kv7 通道抑制均诱导强烈的 Ca ²⁺振荡，在 Kv7 通道激活剂、瑞替加滨、L 型 Ca ²⁺通道抑制剂、硝苯地平，或 T 型 Ca ²⁺通道抑制剂，NNC 55-0396，在 A7r5 细胞中。使用 FluoVolt 测量的膜电位表现出缓慢的去极化，随后响应 XE991 出现突然的尖峰；^{尖峰与Ca 2+}振荡在时间上相关。磷脂酶 C 抑制剂（edelfosine）可减少 AVP 诱导的 Ca 2+ 振荡，但不会减少 XE991 诱导的 Ca ²⁺振荡。AVP 和 XE991 诱导人 IMA 中[Ca ²⁺ ] _i大幅增加，瑞替加滨、硝苯地平和 NNC 55-0396 也可减弱这种增加。RT-PCR、免疫组织化学和电生理学表明，Kv7.5 是大鼠和人动脉 SMC 中的主要 Kv7 亚基；CACNA1C（Cav1.2；L型）和CACNA1 G （Cav3.1；T型）是两种类型的VSMC中最丰富的电压门控Ca ^{2+通道基因转录本。}本研究确立 Kv7 通道作为VSMC 中Ca ^{2+信号传导的关键调节因子，其中 Kv7.5 发挥主导作用。}