Nicotinic receptors modulating ACh release in rat cortical synaptosomes: role of Ca2+ ions in their function and desensitization

Neurochem Int. 1999 Apr;34(4):319-28. doi: 10.1016/s0197-0186(99)00015-7.


Cholinergic nerve terminals in the central nervous system are endowed with both muscarinic and nicotinic autoreceptors, mediating inhibition, and enhancement of acetylcholine release, respectively. Exogenous acetylcholine inhibited the K+(15 mM)-evoked overflow of [3H]acetylcholine from superfused rat neocortical synaptosomes; however, in the presence of atropine, this muscarinic inhibition was reversed into a nicotinic potentiation when acetylcholine was added concomitantly with high-K+, but not before depolarization. Increasing concentrations of acetylcholine (plus atropine), nicotine and (+)-anatoxin-a produced elevations of the K+-evoked [3H]acetylcholine overflow resulting in bell-shaped concentration-response curves. Synaptosomes pretreated with different concentrations (10 microM to 0.001 microM) of acetylcholine or nicotine responded to a subsequent nicotinic stimulus (10 microM acetylcholine plus 0.1 microM atropine, in 15 mM K+) in a manner reflecting varying degrees of desensitization. This desensitization could be reversed by washings with standard medium and desensitization was attenuated when external Ca2+ ([Ca2+]e) was decreased. Lowering of [Ca2+]e or chelation of internal Ca2+ with 1,2-bis(2-aminophenoxy)ethone-N,N,N',N'-tetracetic acid acetoxymethylester (BAPTA-AM) permitted the nicotinic response to acetylcholine alone (no atropine added) to prevail over the muscarinic response. Pretreatment with BAPTA-AM could however not prevent desensitization by acetylcholine (10 or 0.001 microM). The data indicate that Ca2+ ions are involved in determining the balance between muscarinic and nicotinic autoreceptor function and in the desensitization of nicotinic autoreceptors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholine / metabolism*
  • Acetylcholine / pharmacology
  • Animals
  • Atropine / pharmacology
  • Calcium Channels / physiology
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / metabolism*
  • Cerebral Cortex / physiology
  • Electric Stimulation
  • In Vitro Techniques
  • Kinetics
  • Male
  • Membrane Potentials / drug effects
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Nicotinic / drug effects
  • Receptors, Nicotinic / metabolism*
  • Receptors, Nicotinic / physiology
  • Synaptosomes / drug effects
  • Synaptosomes / metabolism*
  • Synaptosomes / physiology


  • Calcium Channels
  • Receptors, Nicotinic
  • Atropine
  • Acetylcholine