Modulation of transmitter release by action potential duration at the hippocampal CA3-CA1 synapse

J Neurophysiol. 1999 Jan;81(1):288-98. doi: 10.1152/jn.1999.81.1.288.


Presynaptic Ca2+ influx through voltage-dependent Ca2+ channels triggers neurotransmitter release. Action potential duration plays a determinant role in the dynamics of presynaptic Ca2+ influx. In this study, the presynaptic Ca2+ influx was optically measured with a low-affinity Ca2+ indicator (Furaptra). The effect of action potential duration on Ca2+ influx and transmitter release was investigated. The K+ channel blocker 4-aminopyridine (4-AP) was applied to broaden the action potential and thereby increase presynaptic Ca2+ influx. This increase of Ca2+ influx appeared to be much less effective in enhancing transmitter release than raising the extracellular Ca2+ concentration. 4-AP did not change the Ca2+ dependence of transmitter release but instead shifted the synaptic transmission curve toward larger total Ca2+ influx. These results suggest that changing the duration of Ca2+ influx is not equivalent to changing its amplitude in locally building up an effective Ca2+ concentration near the Ca2+ sensor of the release machinery. Furthermore, in the presence of 4-AP, the N-type Ca2+ channel blocker omegaCgTx GVIA was much less effective in blocking transmitter release. This phenomenon was not simply due to a saturation of the release machinery by the increased overall Ca2+ influx because a similar reduction of Ca2+ influx by application of the nonspecific Ca2+ channel blocker Cd2+ resulted in much more inhibition of transmitter release. Rather, the different potencies of omega-CgTx GVIA and Cd2+ in inhibiting transmitter release suggest that the Ca2+ sensor is possibly located at a distance from a cluster of Ca2+ channels such that it is sensitive to the location of Ca2+ channels within the cluster.

Publication types

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

MeSH terms

  • 4-Aminopyridine / pharmacology
  • Action Potentials / drug effects
  • Action Potentials / physiology
  • Adenosine / pharmacology
  • Animals
  • Calcium Channel Blockers / pharmacology
  • Calcium Channels / physiology
  • Excitatory Postsynaptic Potentials / drug effects
  • Excitatory Postsynaptic Potentials / physiology
  • Hippocampus / drug effects
  • Hippocampus / physiology*
  • In Vitro Techniques
  • Male
  • Neurotransmitter Agents / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Presynaptic / drug effects
  • Receptors, Presynaptic / physiology
  • Synapses / drug effects
  • Synapses / physiology*


  • Calcium Channel Blockers
  • Calcium Channels
  • Neurotransmitter Agents
  • Receptors, Presynaptic
  • 4-Aminopyridine
  • Adenosine