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Receptor‐coupled, DAG‐gated Ca 2+ ‐permeable cationic channels in LNCaP human prostate cancer epithelial cells
Author(s) -
Sydorenko V.,
Shuba Y.,
Thebault S.,
Roudbaraki M.,
Lepage G.,
Prevarskaya N.,
Skryma R.
Publication year - 2003
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1111/j.1469-7793.2003.00823.x
Subject(s) - lncap , chemistry , trpc1 , trpc , trpc3 , receptor , transient receptor potential channel , biophysics , prostate cancer , endocrinology , microbiology and biotechnology , medicine , biology , biochemistry , cancer
Although the prostate gland is a rich source of α1‐adreno‐ (α1‐AR) and m1‐cholino receptors (m1‐AChR), the membrane processes associated with their activation in glandular epithelial cells is poorly understood. We used the whole‐cell patch‐clamp technique to show that the agonists of the respective receptors, phenylephrine (PHE) and carbachol (CCh), activate cationic membrane currents in lymph node carcinoma of the prostate (LNCaP) human prostate cancer epithelial cells, which are not dependent on the filling status of intracellular IP 3 ‐sensitive Ca 2+ stores, but directly gated by diacylglycerol (DAG), as evidenced by the ability of its membrane permeable analogue, OAG, to mimic the effects of the agonists. The underlying cationic channels are characterized by the weak field‐strength Eisenman IV permeability sequence for monovalent cations ( P K (25) > P Cs (4.6) > P Li (1.4) > P Na (1.0)), and the following permeability sequence for divalent cations: P Ca (1.0) > P Mg (0.74) > P Ba (0.6) > P Sr (0.36) > P Mn (0.3). They are 4.3 times more permeable to Ca 2+ than Na + and more sensitive to the inhibitor 2‐APB than SK&F 96365. RT‐PCR analysis shows that DAG‐gated members of the transient receptor potential (TRP) channel family, including TRPC1 and TRPC3, are present in LNCaP cells. We conclude that, in prostate cancer epithelial cells, α1‐ARs and m1‐AChRs are functionally coupled to Ca 2+ ‐permeable DAG‐gated cationic channels, for which TRPC1 and TRPC3 are the most likely candidates.