Nicotine induces calcium spikes in single nerve terminal varicosities: A role for intracellular calcium stores

Keith Brain, SJ Trout, VM Jackson, N Dass, TC Cunnane

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While nicotine is known to act at neuronal nicotinic acetylcholine receptors (nAChRs) to facilitate neurotransmitter release, the mechanisms underlying this action are poorly understood. Some of its effects are known to be mediated by presynaptic receptors. In the mouse vas deferens nicotine (10-30 muM) transiently increased the force of neurogenic contraction by 135 +/- 25%, increased the amplitude of excitatory junction potentials by 74 +/- 6% and increased the frequency of spontaneous excitatory junction potentials in four out of six preparations. Confocal microscopy and the calcium indicator Oregon Green 488 BAPTA-1 dextran were used to measure calcium concentration changes in the nerve terminals. Nicotine did not affect the action potential-evoked calcium transient but instead triggered small, random fluctuations ('calcium. spikes') in intra-varicosity calcium concentrations at an average frequency of 0.09 +/- 0.02 Hz. These were insensitive to tetrodotoxin at a concentration that blocked action-potential evoked calcium transients (300 nM). They were abolished by the nAChR blocker hexamethonium (100 muM) and by both ryanodine (100 muM) and caffeine (3 mM), agents that modify calcium release from intracellular stores. We propose a novel mechanism whereby nicotine's action at nAChRs triggers calcium-induced calcium release from a ryanodine-sensitive calcium store in nerve terminals. This primes neurotransmitter release mechanisms and enhances both spontaneous and action potential-evoked neurotransmitter release. (C) 2001 IBRO. Published by Elsevier Science Ltd. All rights reserved.
Original languageEnglish
Pages (from-to)395-403
Number of pages9
Issue number2
Publication statusPublished - 1 Jan 2001


  • synaptic transmission
  • mouse
  • vas deferens
  • excitatory junction potentials
  • calcium-induced calcium release (CICR)
  • nicotinic acetylcholine receptor


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