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首页> 外文期刊>American Journal of Physiology >Functional TRPV4 channels are expressed in human airway smooth muscle cells.
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Functional TRPV4 channels are expressed in human airway smooth muscle cells.

机译：功能性TRPV4通道在人气道平滑肌细胞中表达。

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摘要

Hypotonic stimulation induces airway constriction in normal and asthmatic airways. However, the osmolarity sensor in the airway has not been characterized. TRPV4 (also known as VR-OAC, VRL-2, TRP12, OTRPC4), an osmotic-sensitive cation channel in the transient receptor potential (TRP) channel family, was recently cloned. In the present study, we show that TRPV4 mRNA was expressed in cultured human airway smooth muscle cells as analyzed by RT-PCR. Hypotonic stimulation induced Ca(2+) influx in human airway smooth muscle cells in an osmolarity-dependent manner, consistent with the reported biological activity of TRPV4 in transfected cells. In cultured muscle cells, 4alpha-phorbol 12,13-didecanoate (4-alphaPDD), a TRPV4 ligand, increased intracellular Ca(2+) level only when Ca(2+) was present in the extracellular solution. The 4-alphaPDD-induced Ca(2+) response was inhibited by ruthenium red (1 microM), a known TRPV4 inhibitor, but not by capsazepine (1 microM), a TRPV1 antagonist, indicating that 4-alphaPDD-induced Ca(2+) response is mediated by TRPV4. Verapamil (10 microM), an L-type voltage-gated Ca(2+) channel inhibitor, had no effect on the 4-alphaPDD-induced Ca(2+) response, excluding the involvement of L-type Ca(2+) channels. Furthermore, hypotonic stimulation elicited smooth muscle contraction through a mechanism dependent on membrane Ca(2+) channels in both isolated human and guinea pig airways. Hypotonicity-induced airway contraction was not inhibited by the L-type Ca(2+) channel inhibitor nifedipine (1 microM) or by the TRPV1 inhibitor capsazepine (1 microM). We conclude that functional TRPV4 is expressed in human airway smooth muscle cells and may act as an osmolarity sensor in the airway.
机译：低渗刺激在正常和哮喘气道中引起气道收缩。然而，气道中的渗透压传感器尚未被表征。最近克隆了TRPV4（也称为VR-OAC，VRL-2，TRP12，OTRPC4），这是瞬态受体电位（TRP）通道家族中的一种渗透敏感阳离子通道。在本研究中，我们显示，通过RT-PCR分析，TRPV4 mRNA在培养的人气道平滑肌细胞中表达。低渗刺激以渗透压依赖的方式诱导人类气道平滑肌细胞中的Ca（2+）流入，与TRPV4在转染细胞中报道的生物活性一致。在培养的肌肉细胞中，只有当细胞外溶液中存在Ca（2+）时，TRPV4配体4alpha-phorbol 12,13-十二烷酸酯（4-alphaPDD）才会增加细胞内Ca（2+）的水平。 4-alphaPDD诱导的Ca（2+）反应受到钌红（1 microM），一种已知的TRPV4抑制剂的抑制，但不受Capsazepine（1 microM），一种TRPV1拮抗剂的抑制，表明4-al​​phaPDD诱导的Ca（2 +）反应是由TRPV4介导的。维拉帕米（10 microM），L型电压门控Ca（2+）通道抑制剂，对4-alphaPDD诱导的Ca（2+）反应没有影响，除了L型Ca（2+）的参与渠道。此外，低渗刺激通过依赖于孤立的人和豚鼠气道膜Ca（2+）通道的机制引起平滑肌收缩。低渗诱导的气道收缩不受L型Ca（2+）通道抑制剂硝苯地平（1 microM）或TRPV1抑制剂capsazepine（1 microM）的抑制。我们得出结论，功能性TRPV4在人气道平滑肌细胞中表达，并可能在气道中充当渗透压传感器。

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