The primary function of the presynaptic nerve terminal is to release transmitter quanta and thus activate the postsynaptic target cell. In almost every step leading to the release of transmitter quanta, there is a substantial involvement of ion channels. In this review, the multitude of ion channels in the presynaptic terminal are surveyed. There are at least 12 different major categories of ion channels representing several tens of different ion channel types; the number of different ion channel molecules at presynaptic nerve terminals is many hundreds. We describe the different ion channel molecules at the surface membrane and inside the nerve terminal in the context of their possible role in the process of transmitter release. Frequently, a number of different ion channel molecules, with the same basic function, are present at the same nerve terminal. This is especially evident in the cases of calcium channels and potassium channels. This abundance of ion channels allows for a physiological and pharmacological fine tuning of the process of transmitter release and thus of synaptic transmission.

The presynaptic nerve terminal is of key importance in communication in the nervous system. Its primary role is to release transmitter quanta on the arrival of an appropriate stimulus. The structural basis of these transmitter quanta are the synaptic vesicles that fuse with the surface membrane of the nerve terminal, to release their content of neurotransmitter molecules and other vesicular components. We subdivide the control of quantal release into two major classes: the processes that take place before the fusion of the synaptic vesicle with the surface membrane (the pre-fusion control) and the processes that occur after the fusion of the vesicle (the post-fusion control). The pre-fusion control is the main determinant of transmitter release. It is achieved by a wide variety of cellular components, among them the ion channels. There are reports of several hundred different ion channel molecules at the surface membrane of the nerve terminal, that for convenience can be grouped into eight major categories. They are the voltage-dependent calcium channels, the potassium channels, the calcium-gated potassium channels, the sodium channels, the chloride channels, the non-selective channels, the ligand gated channels and the stretch-activated channels. There are several categories of intracellular channels in the mitochondria, endoplasmic reticulum and the synaptic vesicles. We speculate that the vesicle channels may be of an importance in the post-fusion control of transmitter release.

1. Periodic oscillations were detected in the activity of single macromolecules: potassium channels. 2. When potassium channels are repeatedly activated in isolated patches from fused synaptosomes of Torpedo electric organ, their behavior exhibits a departure from random activation. 3. The departure from random behavior is demonstrated by the runs test and by the lack of fit to Poisson distribution. 4. Under appropriate experimental conditions, the channels display periodic oscillations with a periodicity of approximately 20 s when activated at a rate of 1.25 Hz. 5. The oscillations do not arise from sampling, recording, or computational artifacts. 6. It is conceivable that single-channel oscillations play a role in the generation of membrane oscillations and thus may contribute to the oscillatory behavior of the nervous system.

The bursting K+ channel is the most common channel in fused Torpedo presynaptic nerve terminals. It possesses the property of 'statistical memory', demonstrated by non-random probability of channel opening. We examined the voltage dependence of the statistical memory and report that removal of channel inactivation by hyperpolarization abolishes it. Addition of the potassium channel blocker 4-aminopyridine to the bath solution led to disappearance of statistical memory, while raising extracellular potassium concentration had the opposite effect. Another common channel at Torpedo nerve terminals which is a non-selective channel did not exhibit statistical memory. We conclude that statistical memory is a channel-specific phenomenon and speculate regarding its possible role in cellular and network properties of the nervous system.

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