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G proteins activate ionic conductances at multiple sites in T84 cells
1Department of Physiology, School of Medicine, State University of New York at Buffalo, 14214, USA.
The American Journal of Physiology
|April 1, 1997
Summary
G proteins mediate T84 cell ionic currents during cholinergic stimulation. They activate potassium and chloride channels, suggesting a role in calcium signaling and channel gating.
Area of Science:
- Cellular physiology
- Molecular biology
- Ion channel function
Background:
- Cholinergic stimulation in T84 cells involves complex signaling pathways.
- The role of G proteins in regulating ionic conductances requires further elucidation.
Purpose of the Study:
- To investigate the involvement of G proteins in activating ionic conductances in T84 cells.
- To determine the specific roles of G proteins in cholinergic-stimulated ion channel activity.
Main Methods:
- Whole-cell voltage clamp electrophysiology on isolated T84 cells.
- Application of cholinergic agonist carbachol and guanine nucleotide analogues (GDPβS, GTPγS).
- Manipulation of intracellular calcium levels and ionic gradients.
Main Results:
- Carbachol activated oscillating K+ currents, modulated by GDPβS.
- GTPγS induced large oscillating K+ and inward currents, independent of extracellular Ca2+ but dependent on intracellular Ca2+.
- GTPγS also activated oscillating Na+ and Cl- currents under specific ionic conditions.
- Inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] activated K+ currents, suggesting a role for the phospholipase C pathway.
Conclusions:
- G proteins mediate carbachol-induced Ca2+ release via the phospholipase C-Ins(1,4,5)P3 pathway.
- G proteins directly gate Cl- channels, enhancing their Ca2+-sensitivity.
- These findings highlight the critical role of G proteins in regulating T84 cell ionic conductances.