Pore residues of transient receptor potential channels canonical 1 and 4 heteromer determine channel properties

Am J Physiol Cell Physiol. 2023 Jul 1;325(1):C42-C51. doi: 10.1152/ajpcell.00488.2022. Epub 2023 May 22.


Transient receptor potential channels canonical 1 and 4 (TRPC1 and TRPC4) are proteins belonging to the same TRPC channel family, and the two are known to form a heterotetrameric channel. TRPC4 can form a homotetrameric, nonselective cation channel by itself, but the involvement of the TRPC1 subunit changes several major characteristics of the channel. In this study, we focused on the pore region (selectivity filter, pore helix, and S6 helix) of TRPC1 and TRPC4 as a determinant of the identity and characteristics of a heteromeric TRPC1/4 channel: decreased calcium permeability of the channel and outward-rectifying current-voltage (I-V) curve. Mutants and chimeras of the pore residues were created, and their currents were recorded using whole cell patch clamp. The lower gate mutants of TRPC4 exhibited diminished calcium permeability as measured by GCaMP6 fluorescence. Also, chimeric channels substituting the pore region of TRPC1 to TRPC4 were made to locate the pore region that is critical in the production of an outward-rectifying I-V curve characteristic of TRPC1/4 heteromeric channels.NEW & NOTEWORTHY Heteromer research has been a challenging field due to lack of structural studies. Using chimeras and single mutants, we present evidence that the pore region of TRPC1/4 heteromer contributes to determining the channel's characteristics such as calcium permeability, I-V curve, and conductance.

Keywords: TRPC1; TRPC4; heteromeric TRP channels.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Calcium / metabolism
  • Cell Membrane / chemistry
  • HEK293 Cells
  • Humans
  • Ion Channel Gating
  • Models, Molecular
  • Protein Multimerization*
  • Protein Structure, Quaternary
  • Protein Structure, Tertiary
  • TRPC Cation Channels / chemistry


  • Calcium
  • TRPC Cation Channels