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

Presynaptic Ca2+ influx through voltage-dependent Ca2+ channels triggers ne urotransmitter 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 (Fura ptra). The effect of action potential duration on Ca2+ influx and transmitt er release was investigated. The K+ channel blocker 4-aminopyridine (4-AP) was applied to broaden the action potential and thereby increase presynapti c Ca2+ influx. This increase of Ca2+ influx appeared to be much less effect ive in enhancing transmitter release than raising the extracellular Ca2+ co ncentration. 4-AP did not change the Ca2+ dependence of transmitter release but instead shifted the synaptic transmission curve toward larger total Ca 2+ influx. These results suggest that changing the duration of Ca2+ influx is not equivalent to changing its amplitude in locally building up an effec tive Ca2+ concentration near the Ca2+ sensor of the release machinery. Furt hermore, in the presence of 4-AP, the N-type Ca2+ channel blocker omega CgT x GVIA was much less effective in blocking transmitter release. This phenom enon was not simply due to a saturation of the release machinery by the inc reased overall Ca2+ influx because a similar reduction of Ca2+ influx by ap plication of the nonspecific Ca2+ channel blocker Cd2+ resulted in much mor e inhibition of transmitter release. Rather, the different potencies of ome ga-CgTx GVIA and Cd2+ in inhibiting transmitter release suggest that the Ca 2+ 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 clus ter.