Isoform- and receptor-specific channel property of canonical transient receptor potential (TRPC)1/4 channels

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Transient receptor potential canonical (TRPC) 1, the first mammalian homologue of Drosophila trp gene, is distributed widely in mammalian cells and is involved in many physiological functions. TRPC1 is reported to be functional following heteromeric formation with other TRPC channels such as TRPC4 or TRPC5. It is known that the composition of this widely distributed TRPC1 is far from simple; functionality of such channels has been highly controversial. Furthermore, TRPC1 gene is known to have two splicing variants; one encodes long (TRPC1 alpha) and the other encodes short (TRPC1 beta) TRPC1 isoforms, respectively. In this study, we examined the functionality of TRPC1/4 channels using various activation systems. G(q/11)-coupled receptor (e.g., M1 or M3 receptors) stimulation significantly increased TRPC1 alpha/4 currents but induced mild activation of TRPC1 beta/4. In addition, when expressed with TRPC4, TRPC1 alpha acted as a pore-constituting subunit and not a beta ancillary subunit. Multimerized with TRPC4, TRPC1 alpha also generated strong pore field strength. We also found that G(i/o)-coupled receptor (e.g., M2 receptor) stimulation was insufficient to activate TRPC1 alpha/4 and TRPC1 beta/4 channels but selectively activated TRPC4 homomeric channels. These findings demonstrate that TRPC1/4 channel shows dynamic gating property depending on TRPC1 isoform subtypes and receptor stimulation system. Therefore, careful discrimination of the specificity of TRPC1 isoforms and upstream activation system is important in thorough understanding of TRPC1 and TRPC1/4 channels.
Publisher
SPRINGER
Issue Date
2014-03
Language
English
Article Type
Article
Keywords

STORE-OPERATED CHANNEL; SMOOTH-MUSCLE-CELLS; TRPC CHANNELS; HUMAN HOMOLOG; SIGNALING MICRODOMAINS; FUNCTIONAL EXPRESSION; CATION CHANNEL; CA2+ CHANNELS; LIVING CELLS; ACTIVATION

Citation

PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY, v.466, no.3, pp.491 - 504

ISSN
0031-6768
DOI
10.1007/s00424-013-1332-y
URI
http://hdl.handle.net/10203/189828
Appears in Collection
RIMS Journal Papers
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