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ORIGINAL RESEARCH article

Front. Physiol.
Sec. Membrane Physiology and Membrane Biophysics
Volume 15 - 2024 | doi: 10.3389/fphys.2024.1392980
This article is part of the Research Topic Direct Modulation of Ion Channels by G-proteins View all 5 articles

Unique responses of fixed stoichiometric TRPC1-TRPC5 concatemer to G proteins

Provisionally accepted
Hana Kang Hana Kang INSUK SO INSUK SO *
  • Seoul National University, Seoul, Republic of Korea

The final, formatted version of the article will be published soon.

    Transient receptor potential canonical (TRPC)5 channel is a nonselective cation channel that plays a significant role in membrane depolarization and calcium influx. TRPC5 not only forms homotetramers itself but also heterotetramers with TRPC1. However, accurately testing and confirming these heterotetrameric channels at specific ratios has proven challenging. Therefore, creating heteromeric concatemers of TRPC5 and TRPC1 with a fixed stoichiometry of 1:1 becomes essential. This study aims to meticulously identify and reaffirm the properties of TRPC5 homomers and heteromers with a 1:1 fixed stoichiometry, to determine the optimal ratio for the TRPC1/5 heterotetramer. Overall characteristics were consistent with the previous studies, but several specific features were different. The TRPC1-TRPC5 concatemer is activated by Englerin A, but neither carbachol nor constitutively active Gαi protein can trigger its activation. However, carbachol can activate the TRPC1-TRPC5 concatemer when internal GTPγS is present. Meanwhile, the TRPC5-TRPC5 concatemer is responsive to both carbachol and Englerin A. In conclusion, we provide evidence that TRPC1-TRPC5 heteromeric concatemer with fixed stoichiometry need specific condition to respond to carbachol whereas TRPC5-TRPC5 homomeric concatemer responds physiologically to carbachol. Additional research may be necessary to ascertain the optimal stoichiometry for the TRPC1-TRPC5 concatemer to enhance its electrophysiological properties.

    Keywords: TRPC5, TRPC1, heteromer, homomer, Concatemer, G protein, Englerin A, GTPγS

    Received: 28 Feb 2024; Accepted: 17 May 2024.

    Copyright: © 2024 Kang and SO. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: INSUK SO, Seoul National University, Seoul, Republic of Korea

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