Related Experiment Videos
Potential synergy: voltage-driven steps in receptor-G protein coupling and beyond
Thomas B Bolton1, Alexander V Zholos
1Pharmacology and Clinical Pharmacology, St. George's Hospital Medical School, London SW17 0RE, UK. sgkl180@sghms.ac.uk
Science'S STKE : Signal Transduction Knowledge Environment
|December 4, 2003
Summary
G protein-coupled receptor (GPCR) responses, like those of the m2 muscarinic receptor, can be voltage-dependent. This voltage sensitivity is observed even when G proteins are directly activated, suggesting diverse underlying mechanisms.
Area of Science:
- Molecular and Cellular Biology
- Neuroscience
- Physiology
Background:
- G protein-coupled receptors (GPCRs) mediate diverse cellular signaling pathways.
- GPCR responses are typically not considered voltage-dependent.
- Emerging evidence suggests voltage sensitivity in specific GPCR signaling pathways.
Purpose of the Study:
- To investigate the voltage dependence of G protein-coupled receptor signaling.
- To explore the mechanisms underlying voltage sensitivity in GPCRs.
- To highlight examples of voltage-dependent GPCR responses.
Main Methods:
- Electrophysiological recordings in oocytes and mammalian smooth muscle cells.
- Activation of muscarinic receptors with acetylcholine.
- Direct intracellular activation of G proteins using GTPgammaS.
Main Results:
- Oocyte sensitivity to acetylcholine (activating m2 muscarinic receptors) is affected by membrane potential changes.
- M2 receptor-evoked cation currents in smooth muscle cells exhibit strong voltage dependence.
- Voltage dependence persists even when G proteins are directly activated, bypassing the receptor.
Conclusions:
- Certain G protein-coupled receptor responses, particularly involving the m2 muscarinic receptor, demonstrate significant voltage dependence.
- The mechanisms driving voltage sensitivity in GPCR signaling appear to be diverse and context-specific.
- Further research is needed to fully elucidate the molecular basis of voltage-dependent GPCRs.