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Published on: December 31, 2013
Negative self-regulation of transient receptor potential canonical 4 by the specific interaction with phospholipase
Juyeon Ko1, Jinhyeong Kim1, Jongyun Myeong1
1Department of Physiology, Seoul National University College of Medicine, Seoul 03080, Korea.
Abstract:
Transient receptor potential canonical (TRPC) channels are non-selective calcium-permeable cation channels. It is suggested that TRPC4β is regulated by phospholipase C (PLC) signaling and is especially maintained by phosphatidylinositol 4,5-bisphosphate (PIP2). In this study, we present the regulation mechanism of the TRPC4 channel with PIP2 hydrolysis which is mediated by a channel-bound PLCδ1 but not by the GqPCR signaling pathway. Our electrophysiological recordings demonstrate that the Ca2+ via an open TRPC4 channel activates PLCδ1 in the physiological range, and it causes the decrease of current amplitude. The existence of PLCδ1 accelerated PIP2 depletion when the channel was activated by an agonist. Interestingly, PLCδ1 mutants which have lost the ability to regulate PIP2 level failed to reduce the TRPC4 current amplitude. Our results demonstrate that TRPC4 self-regulates its activity by allowing Ca2+ ions into the cell and promoting the PIP2 hydrolyzing activity of PLCδ1.
Insights
Transient receptor potential canonical (TRPC) channels, specifically TRPC4, self-regulate their calcium permeability. This occurs through a mechanism involving calcium influx activating a bound phospholipase Cδ1 (PLCδ1) to hydrolyze phosphatidylinositol 4,5-bisphosphate (PIP2).
Area of Science:
- Cellular Physiology
- Ion Channel Function
- Signal Transduction
Background:
- Transient receptor potential canonical (TRPC) channels are crucial calcium-permeable ion channels.
- TRPC4β activity is linked to phospholipase C (PLC) signaling and phosphatidylinositol 4,5-bisphosphate (PIP2) levels.
Purpose of the Study:
- To elucidate the self-regulation mechanism of TRPC4 channels.
- To investigate the role of PLCδ1 in TRPC4 channel regulation via PIP2 hydrolysis.
Main Methods:
- Electrophysiological recordings to measure TRPC4 channel activity.
- Investigating the interaction between TRPC4, Ca2+, and PLCδ1.
- Utilizing PLCδ1 mutants to assess PIP2 regulation.
Main Results:
- Calcium influx through open TRPC4 channels activates bound PLCδ1.
- Activated PLCδ1 hydrolyzes PIP2, leading to decreased TRPC4 current amplitude.
- PLCδ1 is essential for TRPC4 self-regulation, independent of GqPCR signaling.
Conclusions:
- TRPC4 channels exhibit self-regulation of their activity.
- This self-regulation involves calcium-dependent activation of channel-bound PLCδ1.
- PLCδ1-mediated PIP2 hydrolysis is a key component of TRPC4 channel inactivation.
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