Characteristics of Transmitter Secretion from Individual Sympathetic Varicosities

Abstract

Electrophysiological recording techniques have been developed to study action potential propagation and neurotransmitter release, at the level of the varicosity, in postganglionic sympathetic nerve terminals. Several techniques have been employed, including differentiation of the rising phases of intracellularly recorded excitatory junction potentials (discrete events) and focal extracellular recording of the nerve terminal action potential and associated excitatory junction currents (NTIs, EJCs). This chapter focuses on the majority of this chapter on results obtained using this preparation. Researchers have shown that transmitter release from individual varicosities occurs intermittently following low-frequency nerve stimulation. The probability of transmitter release increases with stimulation frequency, that is, frequency-dependent facilitation. The mechanisms underlying frequency-dependent facilitation remain fairly poorly understood, but it is clear that calcium plays a pivotal role. One surprising finding is that residual release is inhibited by ryanodine in a use- and time-dependent manner, suggesting that this pharmacologically distinct voltage-dependent calcium channel is located close to, or is in some way coupled to, ryanodine receptors (RyRs). Ryanodine receptors are involved in excitation-contraction coupling in cardiac and skeletal muscle but are not thought to play any role in action potential-evoked transmitter release. The critical determinant of neurotransmitter release is an increase in the intraneuronal calcium concentration following invasion of the nerve terminal by the action potential. This transient increase in the intraneuronal calcium level is thought to arise solely by calcium entering through clusters of voltage-dependent calcium channels located close to the sites of neurotransmitter release, that is, active zones.