Expression of transient receptor potential C6 and related transient receptor potential family members in human airway smooth muscle and lung tissue.
Elevation of the intracellular free Ca(2+) concentration regulates many functional responses in airway smooth muscle, including contraction, proliferation, adhesion, and cell survival. This increase in calcium can be achieved by a release from internal stores (sarcoplasmic reticulum) and/or entry across the cell membrane from the extracellular environment. The molecular identity of this calcium influx pathway in human airway smooth muscle (HASM) remains unclear. Functional studies using Fluo 4-loaded HASM suggest the presence of a histamine H(1) receptor-activated Ca(2+) entry pathway with characteristics similar to those seen with transient receptor potential (TRP) family homologs. Using a range of molecular and cell biological approaches we defined the expression pattern of transient receptor potential classics (TRPC) homologs in airway cells and tissue. Here we show that HASM and human bronchial epithelial cells both express TRPC1, -4, and -6, with HASM also expressing TRPC3 at the mRNA level. Identification of TRPC6 protein by western blot and confocal microscopy indicated that the protein is localized in specific cell types, suggesting that it plays an important role in regulating key functions in airway cells. These data demonstrate the expression of a range of TRPC homologs in the airway and the presence of a functional Ca(2+) entry pathway with characteristics typical of TRPC family members. TRPC homologs may provide an important novel target for the treatment of airway disease.
Corteling
Randolph L
RL
Division of Therapeutics, University Hospital, Queens Medical Centre, Nottingham NG7 2UH, UK.
Li
Su
S
Giddings
June
J
Westwick
John
J
Poll
Chris
C
Hall
Ian P
IP
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology; D002460:Cell Line; D006801:Humans; D008168:Lung / Q000166:cytology / Q000378:metabolism*; D005810:Multigene Family; D009130:Muscle, Smooth / Q000378:metabolism*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D011817:Rabbits; D020545:Respiratory Mucosa / Q000166:cytology / Q000378:metabolism; D013050:Spectrometry, Fluorescence; D050052:TRPC Cation Channels; D000074287:TRPC6 Cation Channel
D015220:Calcium Channels; D020033:Protein Isoforms; D050052:TRPC Cation Channels; D000074287:TRPC6 Cation Channel; C117032:TRPC6 protein, human; D002118:Calcium