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Effects of morphine on ionic currents in frog node of Ranvier
Abstract:
The effects of externally or internally applied morphine hydrochloride on the node of Ranvier of the frog were studied under current and voltage clamp conditions. Externally applied morphine in a concentration of 0.5-1 mM prolonged the action potential and the absolute refractory period. It inhibited the repetitive response of sensory fibres to long-lasting depolarizing pulses. Externally applied morphine was more effective in depressing the steady state K current than the peak Na current. When added to the internal medium (by diffusion from the cut ends of the fibre) morphine had a stronger effect on the peak Na current. Morphine did not alter the kinetics of Na activation but increased the time constants of development or removal of Na inactivation by a factor of about 1.2. Morphine reduced both the fast and slow phase of the inward K tail currents recorded in Ringer with 30 mM K. Of the two components (gKf1 and gKf2) of fast K conductance described by J.M. Dubois (1981, J. Physiol. 318, 297) only gKf2 was affected. The morphine antagonist naloxone in a concentration of 0.1 mM completely and reversibly abolished the component gKf2 of the fast K conductance. Naloxone did not antagonize the effect of morphine. These findings show that there are no specific opiate receptors in the membrane of peripheral nerves.
Insights
Morphine affects frog nerve cells by altering electrical activity and ion currents. However, the antagonist naloxone did not block these effects, suggesting no specific opiate receptors are involved in peripheral nerves.
Area of Science:
- Neuroscience
- Pharmacology
- Cellular Electrophysiology
Background:
- Morphine is known for its analgesic properties, primarily acting on the central nervous system.
- The effects of morphine on peripheral nerve function, specifically the node of Ranvier, are not well understood.
Purpose of the Study:
- To investigate the electrophysiological effects of morphine hydrochloride on the frog node of Ranvier.
- To determine if morphine's actions on peripheral nerves involve specific opiate receptors.
Main Methods:
- Utilized current and voltage clamp techniques to study the node of Ranvier in frog nerve fibers.
- Applied morphine hydrochloride externally and internally, and assessed its impact on action potentials and ion currents.
- Investigated the effects of the morphine antagonist naloxone.
Main Results:
- Externally applied morphine prolonged action potentials and absolute refractory periods, and inhibited repetitive responses.
- Morphine depressed steady-state potassium (K) current more than peak sodium (Na) current when applied externally.
- Internally applied morphine had a greater effect on peak Na current, altering Na inactivation kinetics.
- Morphine reduced both fast and slow components of inward K tail currents, specifically affecting the gKf2 component.
- Naloxone abolished the gKf2 component but did not antagonize morphine's effects.
Conclusions:
- Morphine significantly alters the electrical excitability and ion channel function of the frog node of Ranvier.
- The observed effects of morphine on peripheral nerves are not mediated by specific opiate receptors.
- These findings contribute to understanding the peripheral actions of opioids beyond their central effects.