TRPC5 channels undergo changes in gating properties during the activation-deactivation cycle.
Alexander G Obukhov1, Martha C Nowycky
1Department Pharmacology & Physiology, UMDNJ, New Jersey Medical School, Newark, New Jersey 07103, USA.
Journal of Cellular Physiology
|February 6, 2008
Summary
Transient Receptor Potential Canonical 5 (TRPC5) channels exhibit dynamic gating, switching between voltage-dependent and independent states. This phase transition is modulated by ions and proteins, revealing novel regulatory mechanisms for TRPC5 channel activity.
Area of Science:
- Molecular Biology
- Ion Channel Physiology
- Cellular Signaling
Background:
- Transient Receptor Potential Canonical 5 (TRPC5) are non-specific cation channels activated via phospholipase C-dependent pathways.
- The precise gating mechanism and voltage-dependent properties of TRPC5 channels remain incompletely understood.
- TRPC5 current-voltage relationships (I-Vs) exhibit dynamic changes during activation and deactivation cycles.
Purpose of the Study:
- To investigate the gating mechanisms underlying the observed changes in TRPC5 channel I-V relationships.
- To determine if distinct biophysical characteristics correlate with different I-V shapes ('phases') of TRPC5 currents.
- To explore the role of voltage-dependence and modulation by external agents in TRPC5 channel regulation.
Main Methods:
- Patch-clamp recordings were performed on rat TRPC5 transfected HEK293 cells.
- Analysis of TRPC5 current-voltage relationships (I-Vs) during activation-deactivation cycles.
- Single channel recordings and site-directed mutagenesis (D633) were employed.
Main Results:
- TRPC5 currents displayed distinct biophysical characteristics ('phases') with varying I-V shapes (outwardly rectifying, doubly rectifying).
- TRPC5 channels reversibly switched between voltage-dependent and voltage-independent states.
- La3+ ions potentiated inward currents by promoting a phase transition, and mutation of D633 affected channel activity.
Conclusions:
- TRPC5 channel gating is dynamic, with reversible transitions between voltage-dependent and independent states.
- Modulation of these phase transitions by agents like La3+ and EBP50 offers a novel regulatory mechanism for TRPC5 channel activity.
- Understanding TRPC5 gating is crucial for elucidating its role in cellular signaling pathways.
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