Related Experiment Video

Updated: Jan 9, 2026

Expression and Purification of the Human Lipid-sensitive Cation Channel TRPC3 for Structural Determination by Single-particle Cryo-electron Microscopy
08:27

Expression and Purification of the Human Lipid-sensitive Cation Channel TRPC3 for Structural Determination by Single-particle Cryo-electron Microscopy

Published on: January 7, 2019

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Impact of C-Terminal PKC Phosphorylation on TRPC6 Current Kinetics

Maximilian Keck1, Sebastian Pöll1, Hannah Schmelzer1

  • 1Walther Straub Institute of Pharmacology and Toxicology, Ludwig Maximilian University of Munich, 80336 Munich, Germany.

International Journal of Molecular Sciences
|December 11, 2025
PubMed

Insights

Protein kinase C (PKC) phosphorylation of Transient Receptor Potential Canonical 6 (TRPC6) channels fine-tunes their activity. Modifying PKC sites on TRPC6 channels impacts their gating kinetics and conductance, offering insights into drug development for related diseases.

Area of Science:

  • Molecular Biology
  • Cell Physiology
  • Pharmacology

Background:

  • Transient Receptor Potential Canonical 6 (TRPC6) channels are crucial ion channels implicated in kidney, lung, and neurological diseases.
  • TRPC6 channels are activated by diacylglycerol (DAG) and regulated by protein kinase C (PKC) phosphorylation.
  • Understanding TRPC6 regulation is vital for developing targeted therapeutics.

Purpose of the Study:

  • To investigate the functional impact of putative PKC phosphorylation sites in the C-terminus of TRPC6 channels.
  • To determine how PKC-dependent phosphorylation influences TRPC6 channel gating kinetics and conductance.

Main Methods:

  • Whole-cell patch-clamp recordings were employed to analyze TRPC6 channel activity.
  • Photopharmacology using photoswitchable TRPC6 activators (OptoBI-1, OptoDArG) enabled precise kinetic analysis.
  • Site-directed mutagenesis was used to alter putative PKC phosphorylation sites, and PKC activity was pharmacologically modulated.

Main Results:

  • Mutations at C-terminal PKC sites and pharmacological modulation of PKC activity altered TRPC6 current kinetics (activation, inactivation, deactivation).
  • Changes in normalized slope conductances were observed, indicating altered channel properties.
  • These effects were evident even when maximal current density amplitudes remained unchanged, highlighting kinetic and conductance modulation.

Conclusions:

  • PKC-dependent phosphorylation of TRPC6 channels fine-tunes their gating kinetics and conductance in an activator-specific manner.
  • C-terminal phosphorylation sites play a significant role in regulating TRPC6 channel function.
  • These findings provide a deeper understanding of TRPC6 channel regulation, crucial for designing novel modulators for therapeutic applications.
Keywords:
PKC phosphorylationTRPC6 channelscurrent kineticsphotopharmacologyphotoswitchable activators

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