The Journal of Neurophysiology Vol. 81 No. 1 January 1999, pp. 288-298
Copyright ©1999 The American Physiological Society

Modulation of Transmitter Release by Action Potential Duration at the Hippocampal CA3-CA1 Synapse

Jing Qian and Peter Saggau

Division of Neuroscience, Baylor College of Medicine, Houston, Texas

Qian, Jing and Peter Saggau. Modulation of transmitter release by action potential duration at the hippocampal CA3-CA1 synapse. J. Neurophysiol. 81: 288-298, 1999. 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 CgTx 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 -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.

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