Isoform- and receptor-specific channel property of canonical transient receptor potential (TRPC)1/4 channels.
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 (TRPC1α) and the other encodes short (TRPC1β) TRPC1 isoforms, respectively. In this study, we examined the functionality of TRPC1/4 channels using various activation systems. Gq/11-coupled receptor (e.g., M1 or M3 receptors) stimulation significantly increased TRPC1α/4 currents but induced mild activation of TRPC1β/4. In addition, when expressed with TRPC4, TRPC1α acted as a pore-constituting subunit and not a β ancillary subunit. Multimerized with TRPC4, TRPC1α also generated strong pore field strength. We also found that Gi/o-coupled receptor (e.g., M2 receptor) stimulation was insufficient to activate TRPC1α/4 and TRPC1β/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.
Department of Chemistry, Korea Advanced Institute of Science and Technology, Daejeon, 305-701, Republic of Korea.
Jinsung
J
Kim
Misun
M
Kwak
Jae-Pyo
JP
Jeon
Jongyun
J
Myeong
Jinhong
J
Wie
Chansik
C
Hong
Sung-Young
SY
Kim
Ju-Hong
JH
Jeon
Hyun Jin
HJ
Kim
Insuk
I
So
D000200:Action Potentials; D000595:Amino Acid Sequence; D057809:HEK293 Cells; D006801:Humans; D008969:Molecular Sequence Data; D011485:Protein Binding; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D055503:Protein Multimerization; D021381:Protein Transport; D043585:Receptor, Muscarinic M2 / Q000378:metabolism; D050052:TRPC Cation Channels / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
D020033:Protein Isoforms; D043585:Receptor, Muscarinic M2; D050052:TRPC Cation Channels; C489571:TRPC4 ion channel; C096351:transient receptor potential cation channel, subfamily C, member 1