Presynaptic inhibition of synaptic transmission in the rat hippocampus by activation of muscarinic receptors: involvement of presynaptic calcium influx

Br J Pharmacol. 1997 Oct;122(3):511-9. doi: 10.1038/sj.bjp.0701400.


1. Modulation of presynaptic voltage-dependent calcium channels (VDCCs) by muscarinic receptors at the CA3-CA1 synapse of rat hippocampal slices was investigated by using the calcium indicator fura-2. Stimulation-evoked presynaptic calcium transients ([Ca(pre)]t) and field excitatory postsynaptic potentials ( were simultaneously recorded. The relationship between presynaptic calcium influx and synaptic transmission was studied. 2. Activation of muscarinic receptors inhibited [Ca(pre)]t, thereby reducing synaptic transmission. Carbachol (CCh, 10 microM) inhibited [Ca(pre)]t by 35% and reduced fe.p.s.p. by 85%. The inhibition was completely antagonized by 1 microM atropine. An approximate 4th power relationship was found between presynaptic calcium influx and postsynaptic responses. 3. Application of the N-type VDCC-blocking peptide toxin omega-conotoxin GVIA (omega-CTx GVIA, 1 microM) inhibited [Ca(pre)]t and by 21% and 49%, respectively, while the P/Q-type VDCC blocker omega-agatoxin IVA (omega)-Aga IVA, 1 microM) reduced [Ca(pre)]t and by 35% and 85%, respectively. 4. Muscarinic receptor activation differentially inhibited distinct presynaptic VDCCs. Omega-CTx GVIA-sensitive calcium channels were inhibited by muscarinic receptors, while omega-Aga IVA-sensitive channels were not. The percentage inhibition of omega-CTx GVIA-sensitive [Ca(pre)]t was about 63%. 5. Muscarinic receptors inhibited presynaptic VDCCs in a way similar to adenosine (Ad) receptors. The percentage inhibition of omega-CTx GVIA-sensitive [Ca(pre)]t by Ad (100 microM) was about 59%. There was no significant inhibition of omega-Aga IVA-sensitive channels by Ad. The inhibitions of [Ca(pre)]t by CCh and Ad were mutually occlusive. 6. These results indicate that inhibition of synaptic transmission by muscarinic receptors is mainly the consequence of a reduction of the [Ca(pre)]t due to inhibition of presynaptic VDCCs.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Atropine / pharmacology
  • Calcium / metabolism*
  • Calcium Channel Blockers / pharmacology
  • Carbachol / pharmacology
  • Excitatory Postsynaptic Potentials / drug effects
  • Fura-2 / pharmacology
  • Hippocampus / drug effects*
  • Hippocampus / metabolism
  • Hippocampus / physiology
  • In Vitro Techniques
  • Neural Inhibition*
  • Peptides / pharmacology
  • Presynaptic Terminals / physiology*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Muscarinic / drug effects
  • Receptors, Muscarinic / metabolism
  • Receptors, Muscarinic / physiology*
  • Spider Venoms / pharmacology
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology*
  • omega-Agatoxin IVA
  • omega-Conotoxin GVIA


  • Calcium Channel Blockers
  • Peptides
  • Receptors, Muscarinic
  • Spider Venoms
  • omega-Agatoxin IVA
  • Atropine
  • Carbachol
  • omega-Conotoxin GVIA
  • Calcium
  • Fura-2