Control of neurotransmitter release by presynaptic waveform at the granule cell to Purkinje cell synapse

The effect of changes in the shape of the presynaptic action potential on neurotransmission was examined at synapses be-tween granule and Purkinje cells in slices from the rat cerebel-lum. Low concentrations of tetraethylammonium were used to broaden the presynaptic action potential. The presynaptic waveform was monitored with voltage-sensitive dyes, the time course and amplitude of presynaptic calcium entry were deter-mined with fluorescent calcium indicators, and EPSCs were measured with a whole-cell voltage clamp. Spike broadening increased calcium influx primarily by prolonging calcium entry without greatly affecting peak presynaptic calcium currents, indicating that the majority of calcium channels reach maximal probability of opening in response to a single action potential and that spike broadening increases the open time of these channels. EPSCs were exquisitely sensitive to elevations o