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Published on: May 19, 2017
Thyrotropin-releasing hormone activates KCa channels in gastric smooth muscle cells via intracellular Ca2+ release
P S Petkova-Kirova1, L T Lubomirov, H S Gagov
1Institute of Biophysics, Bulgarian Academy of Sciences, Sofia.
Abstract:
Thyrotropin-releasing hormone (TRH) is released in high concentrations into gastric juice, but its direct effect on gastric smooth muscles has not been studied yet. We undertook studies on TRH effect on gastric smooth muscle using contraction and patch clamp methods. TRH was found to inhibit both acetylcholine- and BaCl2-induced contractions of gastric strips. TRH, applied to single cells, inhibited the voltage-dependent Ca2+ currents and activated the whole-cell K+ currents. The TRH-induced changes in K+ currents and membrane potential were effectively abolished by inhibitors of either intracellular Ca2+ release channels or phospholipase C. Neither activators, nor blockers of protein kinase C could affect the action of TRH on K+ currents. In conclusion, TRH activates K+ channels via inositol-1,4,5-trisphosphate-induced release of Ca2+ in the direction to the plasma membrane, which in turn leads to stimulation of the Ca2+-sensitive K+ conductance, membrane hyperpolarization and relaxation. The data imply that TRH may act physiologically as a local modulator of gastric smooth muscle tone.
Insights
Thyrotropin-releasing hormone (TRH) inhibits gastric smooth muscle contractions by activating potassium channels. This research reveals TRH
Area of Science:
- Gastroenterology
- Neuroendocrinology
- Smooth Muscle Physiology
Background:
- Thyrotropin-releasing hormone (TRH) is present in gastric juice.
- Its direct effects on gastric smooth muscle remain uninvestigated.
Purpose of the Study:
- To investigate the direct effects of TRH on gastric smooth muscle.
- To elucidate the cellular mechanisms underlying TRH's action on gastric smooth muscle.
Main Methods:
- Contraction studies on gastric strips.
- Patch clamp electrophysiology on single smooth muscle cells.
- Pharmacological manipulation using channel inhibitors and signaling pathway modulators.
Main Results:
- TRH inhibited acetylcholine- and BaCl2-induced gastric contractions.
- TRH inhibited voltage-dependent Ca2+ currents and activated whole-cell K+ currents in single cells.
- TRH's effects on K+ currents and membrane potential were dependent on intracellular Ca2+ release and phospholipase C activity, but not protein kinase C.
Conclusions:
- TRH activates K+ channels through inositol-1,4,5-trisphosphate-mediated Ca2+ release, leading to hyperpolarization and relaxation.
- TRH may function physiologically as a local regulator of gastric smooth muscle tone.
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