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[Morphine decreases the voltage sensitivity of the slow sodium channels]
B V Krylov1, A V Derbenev, S A Podzorova
1Pavlov Institute of Physiology, Russian Academy of Sciences, St. Petersburg, Russia.
Abstract:
Morphine was shown to decrease in a dose-dependent manner the effective charge transfer in tetrodotoxin-resistant (TTXr) sodium channel activation system in short-term cultured dorsal root ganglion cells. Morphine seems to interact with opioid receptors because of total block of the binding by naloxone and naltrexone. Neither activating, nor inhibiting G-protein agents exerted any effect on this process. The morphine signal was blocked by extracellular application of 2 x 10(-4) M ouabain. The findings suggest existence of sodium signalling pathway involving receptors, Na+, K(+)-ATPase and the TTXr sodium channels.
Insights
Morphine reduces sodium channel activity in dorsal root ganglion cells, suggesting a novel sodium signaling pathway. This pathway involves opioid receptors and the Na+, K+-ATPase, impacting pain signaling.
Area of Science:
- Neuroscience
- Pharmacology
- Cell Biology
Background:
- Opioid receptors are known targets for pain management.
- Sodium channels play a critical role in neuronal excitability and signal transduction.
- The interaction between opioid signaling and sodium channels is not fully elucidated.
Purpose of the Study:
- To investigate the effect of morphine on tetrodotoxin-resistant (TTXr) sodium channels.
- To explore the potential involvement of opioid receptors and Na+, K+-ATPase in morphine's action on sodium channels.
- To identify a novel sodium signaling pathway influenced by morphine.
Main Methods:
- Short-term cultured dorsal root ganglion cells were utilized.
- Dose-dependent effects of morphine on charge transfer in TTXr sodium channel activation were measured.
- The role of opioid receptors was assessed using naloxone and naltrexone.
- The involvement of G-proteins was tested using specific activating and inhibiting agents.
- The Na+, K+-ATPase was investigated through extracellular ouabain application.
Main Results:
- Morphine decreased effective charge transfer in TTXr sodium channel activation in a dose-dependent manner.
- Naloxone and naltrexone completely blocked morphine's effect, indicating opioid receptor interaction.
- Neither G-protein activating nor inhibiting agents affected the morphine-induced process.
- Extracellular ouabain (2 x 10(-4) M) blocked the morphine signal, implicating Na+, K+-ATPase.
Conclusions:
- Morphine modulates TTXr sodium channel activity through a mechanism involving opioid receptors.
- A sodium signaling pathway comprising opioid receptors, Na+, K+-ATPase, and TTXr sodium channels is suggested.
- This pathway may represent a novel mechanism for morphine's effects on neuronal function and pain perception.