Functional TRPV4 channels are expressed in human airway smooth muscle cells - PubMed (original) (raw)
. 2004 Aug;287(2):L272-8.
doi: 10.1152/ajplung.00393.2003. Epub 2004 Apr 9.
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- PMID: 15075247
- DOI: 10.1152/ajplung.00393.2003
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Functional TRPV4 channels are expressed in human airway smooth muscle cells
Yanlin Jia et al. Am J Physiol Lung Cell Mol Physiol. 2004 Aug.
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Abstract
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.
Comment in
- A possible role for TRPV4 receptors in asthma.
Liedtke W, Simon SA. Liedtke W, et al. Am J Physiol Lung Cell Mol Physiol. 2004 Aug;287(2):L269-71. doi: 10.1152/ajplung.00153.2004. Am J Physiol Lung Cell Mol Physiol. 2004. PMID: 15246981 Review. No abstract available.
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