The voltage-dependence of transmitter release

In this paper we summarize voltage clamp experiments characterizing transmission at the squid giant synapse. The overall goal of these experiments was to determine a synaptic transfer curve relating presynaptic Ca currents (ICa) to resultant postsynaptic responses. Here we focus on interpreting the phenomenon of transfer curve "hysteresis", which has been proposed to result from an intrinsic voltage-dependence of the transmitter release process. One potential problem in analyzing transfer curves comes from contamination of presynaptic Ca currents by outward currents. Linear leakage currents can be measured and taken into account, but after such corrections ICa measurements at positive potentials are still distorted by outward currents. The presence of residual outward currents at positive potentials results in a voltage-dependent bias in ICa measurement and probably contributes to transfer curve hysteresis. A pharmacological procedure which subtracts currents other than those flowing through Ca channels can be used to circumvent this bias in ICa measurement. Gradients in membrane potential along a nominally voltage clamped presynaptic terminal can allow inappropriate release of transmitter from poorly clamped regions of the terminal. Release from such regions may also contribute to transfer-curve hysteresis when standard voltage clamp methods are employed. A method of localized Ca application which restricts transmitter release to well-clamped presynaptic regions can be used to avoid this problem. Transfer curves measured using refined procedures for ICa measurement and suppression of voltage gradient effects on release exhibit little hysteresis.(ABSTRACT TRUNCATED AT 250 WORDS)