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Ca(2+) elevation evoked by membrane depolarization regulates G protein cycle via RGS proteins in the heart
1Department of Pharmacology II , Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
Circulation Research
|November 22, 2001
Summary
Intracellular calcium (Ca2+) increase regulates heart cell signaling by controlling Regulators of G protein signaling (RGS) proteins. This Ca2+-dependent pathway influences G protein activity and muscarinic K+ channel function.
Area of Science:
- Cellular signaling
- Molecular biology
- Cardiology
Background:
- Regulators of G protein signaling (RGS) proteins are crucial for controlling G protein-mediated signals.
- While RGS function is established in vitro, their in situ mechanisms in intact cells remain unclear.
- G protein signaling is vital for numerous cellular functions, including cardiac electrophysiology.
Purpose of the Study:
- To elucidate the in situ mechanism of RGS protein action in intact cardiac cells.
- To investigate the role of intracellular calcium (Ca2+) in regulating RGS protein activity.
- To understand how Ca2+ influences G protein-mediated muscarinic K+ channel function.
Main Methods:
- Studied acetylcholine-induced K+ currents (K(G)) in heart cells.
- Utilized membrane depolarization to evoke intracellular Ca2+ increases.
- Employed calmodulin inhibitors and mutant RGS4 proteins to probe molecular interactions.
Main Results:
- Intracellular Ca2+ increase, evoked by depolarization, modulates RGS action on G protein-activated K(G) channels.
- The phenomenon of K(G) current relaxation during hyperpolarization is dependent on Ca2+.
- Ca2+/calmodulin formation facilitates RGS GTPase activity, reducing available K(G) channels upon depolarization.
Conclusions:
- A novel Ca2+-dependent signaling pathway regulates the G protein cycle via RGS proteins in cardiac cells.
- Ca2+/calmodulin acts as a key mediator, enhancing RGS GTPase activity.
- This pathway likely represents a general mechanism for Ca2+-dependent regulation of G protein signaling.
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