The transient receptor potential vanilloid 4 channel (TRPV4) is a non-selective cation channel that is widely expressed and activated by a range of stimuli. Amongst these stimuli, changes in cell volume feature as a prominent regulator of TRPV4 activity with cell swelling leading to channel activation. In experimental settings based on abrupt introduction of large osmotic gradients, TRPV4 activation requires co-expression of an aquaporin (AQP) to facilitate such cell swelling. However, TRPV4 readily responds to cell volume increase irrespectively of the molecular mechanism underlying the cell swelling and can, as such, be considered a sensor of increased cell volume. In this review, we will discuss the proposed events underlying the molecular coupling from cell swelling to channel activation and present the evidence of direct versus indirect swelling-activation of TRPV4. With this summary of the current knowledge of TRPV4 and its ability to sense cell volume changes, we hope to stimulate further experimental efforts in this area of research to clarify TRPV4’s role in physiology and pathophysiology.

瞬时受体电位香草素 4 通道 (TRPV4) 是一种非选择性阳离子通道，被一系列刺激广泛表达和激活。在这些刺激中，细胞体积的变化是 TRPV4 活性的重要调节因子，细胞肿胀导致通道激活。在基于突然引入大渗透梯度的实验环境中，TRPV4 激活需要水通道蛋白 (AQP) 的共表达以促进此类细胞肿胀。然而，TRPV4 很容易对细胞体积增加做出反应，而不管细胞膨胀的分子机制如何，因此，可以将其视为细胞体积增加的传感器。在这篇综述中，我们将讨论从细胞肿胀到通道激活的分子耦合背后的拟议事件，并提供直接证据相对TRPV4 的间接溶胀激活。通过对 TRPV4 的当前知识及其感知细胞体积变化的能力的总结，我们希望激发该研究领域的进一步实验工作，以阐明 TRPV4 在生理学和病理生理学中的作用。