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Agents that activate protein kinase C reduce acetylcholine sensitivity in cultured myotubes
Abstract:
We have examined acetylcholine (ACh)-elicited potentials or currents in current- or voltage-clamped cultured myotubes exposed to 12-O-tetradecanoyl-phorbol-13-acetate (TPA), a potent tumor promoter that activates protein kinase C. Although this agent had little action on either membrane resting potential or electrical resistance, a reversible decrease in ACh sensitivity was induced on 3-4-d-old chick myotubes. Depression of transmitter action by TPA was extended to 7-8-d mouse myotubes only when they were treated with phosphatidylserine. Glyceryl dioleate had effects on myotubes similar to those of TPA but with a reduced efficacy. We conclude that the activation of protein kinase C might be involved with the capacity of ACh receptors to respond to transmitter stimulation.
Insights
The tumor promoter 12-O-tetradecanoyl-phorbol-13-acetate (TPA) reversibly decreased acetylcholine (ACh) sensitivity in cultured myotubes. This suggests protein kinase C activation may influence ACh receptor function.
Area of Science:
- Neuroscience
- Cell Biology
- Biochemistry
Background:
- Acetylcholine (ACh) is a key neurotransmitter in muscle function.
- Protein kinase C (PKC) is a family of enzymes involved in cell signaling.
- Tumor promoters like 12-O-tetradecanoyl-phorbol-13-acetate (TPA) can activate PKC.
Purpose of the Study:
- To investigate the effect of TPA, a PKC activator, on acetylcholine sensitivity in cultured myotubes.
- To explore the role of PKC in regulating neurotransmitter receptor function.
Main Methods:
- Cultured chick and mouse myotubes were used.
- Electrophysiological techniques (current- and voltage-clamping) were employed.
- Cells were exposed to TPA, phosphatidylserine, and glyceryl dioleate.
Main Results:
- TPA induced a reversible decrease in ACh sensitivity in 3-4-day-old chick myotubes.
- This TPA-induced depression of ACh sensitivity was observed in older mouse myotubes only when co-treated with phosphatidylserine.
- Glyceryl dioleate mimicked TPA's effects but with lower efficacy.
Conclusions:
- Activation of protein kinase C may play a role in modulating the responsiveness of acetylcholine receptors.
- These findings contribute to understanding the cellular mechanisms underlying neurotransmission and potential effects of signaling pathways on receptor function.