The voltage-dependence of transmitter release

Area of Science:

• Neuroscience
• Synaptic Physiology

Background:

• Voltage clamp experiments are crucial for characterizing synaptic transmission.
• Transfer curves, relating presynaptic calcium currents (ICa) to postsynaptic responses, can exhibit hysteresis.
• Hysteresis may arise from voltage-dependence in transmitter release or measurement artifacts.

Purpose of the Study:

• To investigate the phenomenon of transfer curve hysteresis at the squid giant synapse.
• To identify sources of error in presynaptic calcium current (ICa) measurements.
• To develop refined methods for accurate synaptic transfer curve analysis.

Main Methods:

• Voltage clamp electrophysiology on the squid giant synapse.
• Measurement and correction of outward currents contaminating presynaptic calcium currents (ICa).
• Pharmacological isolation of calcium channels and localized calcium application to control release sites.

Main Results:

• Outward currents at positive potentials distort presynaptic calcium current (ICa) measurements, contributing to hysteresis.
• Voltage gradients along the presynaptic terminal also induce release from poorly clamped regions, causing hysteresis.
• Refined ICa measurement and control of voltage gradients significantly reduce transfer curve hysteresis.

Conclusions:

• Transfer curve hysteresis at the squid giant synapse is influenced by measurement artifacts and voltage gradients.
• Accurate characterization of synaptic transmission requires careful control of experimental conditions and precise ICa measurements.
• Improved voltage clamp techniques can yield more reliable synaptic transfer curves.