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TRPM3 channel expression and block in vascular smooth muscle cells
Author(s) -
Naylor Jacqueline,
Li Jing,
Milligan Carol J,
Zeng Fanning,
Porter Karen E,
Beech David J
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.937.6
Subject(s) - vascular smooth muscle , trpm2 , chemistry , trpv4 , calcium channel , microbiology and biotechnology , gene isoform , transient receptor potential channel , calcium , voltage dependent calcium channel , biochemistry , biology , receptor , smooth muscle , endocrinology , gene , organic chemistry
TRPM3 is a calcium‐permeable channel activated by sphingolipids, including D‐ erythro ‐sphingosine (Grimm et al 2005, Mol Pharmacol 67, 798–805). Its cellular functions are largely unknown. Using methods to develop isoform‐specific channel blockers (Xu et al 2005, Nat Biotechnol 23, 1289–93) we produced a TRPM3‐specific blocking agent (TM3E3). Preincubation of cells with TM3E3 produced about 40% block of TRPM3‐mediated calcium‐entry or ionic current. TM3E3 had no effect on the closely related channel TRPM2, or other TRP family members TRPC5 and TRPV4, confirming its specificity for TRPM3. Recently, novel activators for TRPM3 have been suggested. In conjunction with TM3E3, these activators have been used to study a potential role of TRPM3 in human vascular smooth muscle cells. The cells express mRNA encoding TRPM3 and the presence of TRPM3 is indicated by labelling with anti‐TRPM3 antibodies. Sphingosine and its analogues evoked calcium responses that could be inhibited by gadolinium, 2‐APB, TM3E3 or siRNA targeting TRPM3. The data suggest TRPM3 is a novel calcium‐entry channel of vascular smooth muscle cells. The research was supported by a BBSRC Industrial Co‐operative Award in Science and Engineering, the Wellcome Trust and the British Heart Foundation.