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Study on the neuromuscular action of 4-aminopyridine in the mouse diaphragm
W M Fu1, R H Lin, S Y Lin-Shiau
1Department of Pharmacology, College of Medicine, National Taiwan University, Taipei, R.O.C.
Abstract:
4-Aminopyridine (4-AP), in concentrations ranging from 0.01 to 0.3 mM, increased indirectly evoked twitches of mouse diaphragm; directly evoked twitches were unaffected. 4-AP did not significantly affect the resting membrane potential, the amplitude and duration of muscle action potentials, the frequency and amplitude of m.e.p.p.s. or the half decay time of e.p.p.s. and m.e.p.p.s. However, e.p.p. amplitude and quantal content were increased by 4-AP in a concentration-dependent manner. On single stimulation of phrenic nerve 0.1 mM 4-AP induced repetitive e.p.p.s. Although 4-AP did not significantly affect compound action potentials evoked in the phrenic nerve, 4-AP caused repetitive firing to appear in phrenic nerve following single indirect stimulation of the nerve-muscle preparation. This repetitive firing was abolished by d-tubocurarine. In low Ca2+ (0.35 mM) Krebs solution 0.1 mM 4-AP induced muscle fasciculation accompanied by spontaneous giant e.p.p.s. and spontaneous muscle action potentials. In addition, 4-AP (0.1 mM) induced spontaneous repetitive firing of phrenic nerve axons; this was not inhibited by d-tubocurarine.
Insights
4-Aminopyridine (4-AP) enhances neuromuscular transmission by increasing quantal content and causing repetitive firing in nerves. It affects indirectly evoked muscle twitches but not directly evoked ones.
Area of Science:
- Neuroscience
- Pharmacology
- Physiology
Background:
- Neuromuscular transmission relies on acetylcholine release.
- 4-Aminopyridine (4-AP) is known to affect neuronal excitability.
Purpose of the Study:
- To investigate the effects of 4-Aminopyridine (4-AP) on neuromuscular transmission at the mouse diaphragm.
- To elucidate the mechanisms underlying 4-AP's action on nerve-muscle preparations.
Main Methods:
- Electrophysiological recordings of muscle and nerve activity.
- Stimulation of the phrenic nerve and mouse diaphragm preparation.
- Application of varying concentrations of 4-Aminopyridine (4-AP).
Main Results:
- 4-Aminopyridine (4-AP) increased indirectly evoked diaphragm twitches and enhanced end-plate potential (e.p.p.) amplitude and quantal content.
- 0.1 mM 4-AP induced repetitive e.p.p.s and repetitive firing in the phrenic nerve upon single stimulation.
- In low calcium, 4-AP caused muscle fasciculations and spontaneous giant e.p.p.s, along with spontaneous phrenic nerve axon firing.
Conclusions:
- 4-Aminopyridine (4-AP) enhances neurotransmission by increasing quantal release and inducing repetitive neuronal firing.
- The effects of 4-AP are concentration-dependent and influenced by calcium levels.
- 4-AP's action on nerve firing is partly mediated by acetylcholine receptors.