Article date: May 2000
By: T J Searl, E M Silinsky in Volume 130, Issue 2, pages 418-424
The effects of the phosphatidylinositol 4‐kinase inhibitor, phenylarsine oxide (PAO), on acetylcholine (ACh) release and on prejunctional Ca2+ currents were studied at the frog neuromuscular junction using electrophysiological recording techniques.
Application of PAO (30 μM) increased both spontaneous ACh release reflected as miniature end‐plate potential (mepp) frequencies and evoked ACh release reflected as end‐plate potential (epp) amplitudes with a similar time course.
Following the initial increase in epp amplitudes produced by PAO, epps slowly declined and were eventually abolished after approximately 20 min. However, mepp frequencies remained elevated over this time period.
PAO (30 μM) also inhibited the perineural voltage change associated with Ca2+ currents through N‐type Ca2+ channels (prejunctional Ca2+ currents) at motor nerve endings. Addition of British anti‐lewisite (BAL, 1 mM), an inactivator of PAO, partially reversed both the inhibition of epps and the inhibition of the prejunctional Ca2+ current.
The effects of PAO on N‐type Ca2+ channels were investigated more directly using the whole cell patch clamp technique on acutely dissociated sympathetic neurons. Application of PAO (30–40 μM) to these neurons decreased the voltage‐activated calcium currents through N‐type Ca2+ channels, an effect that was partially reversible by BAL.
In combination, these results suggest that inhibition of neurotransmitter release by PAO occurs as a consequence of the inhibition of Ca2+ entry via N‐type calcium channels. The relationship between the effects of PAO on N‐type Ca2+ channels in motor nerve endings and in neuronal soma is discussed.
The effects of the phosphatidylinositol 4‐kinase inhibitor, phenylarsine oxide (PAO), on acetylcholine (ACh) release and on prejunctional Ca2+ currents were studied at the frog neuromuscular junction using electrophysiological recording techniques.
Application of PAO (30 μM) increased both spontaneous ACh release reflected as miniature end‐plate potential (mepp) frequencies and evoked ACh release reflected as end‐plate potential (epp) amplitudes with a similar time course.
Following the initial increase in epp amplitudes produced by PAO, epps slowly declined and were eventually abolished after approximately 20 min. However, mepp frequencies remained elevated over this time period.
PAO (30 μM) also inhibited the perineural voltage change associated with Ca2+ currents through N‐type Ca2+ channels (prejunctional Ca2+ currents) at motor nerve endings. Addition of British anti‐lewisite (BAL, 1 mM), an inactivator of PAO, partially reversed both the inhibition of epps and the inhibition of the prejunctional Ca2+ current.
The effects of PAO on N‐type Ca2+ channels were investigated more directly using the whole cell patch clamp technique on acutely dissociated sympathetic neurons. Application of PAO (30–40 μM) to these neurons decreased the voltage‐activated calcium currents through N‐type Ca2+ channels, an effect that was partially reversible by BAL.
In combination, these results suggest that inhibition of neurotransmitter release by PAO occurs as a consequence of the inhibition of Ca2+ entry via N‐type calcium channels. The relationship between the effects of PAO on N‐type Ca2+ channels in motor nerve endings and in neuronal soma is discussed.
British Journal of Pharmacology (2000) 130, 418–424; doi:10.1038/sj.bjp.0703299
DOI: 10.1038/sj.bjp.0703299
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