9: Signaling at the Nerve-Muscle Synapse: Directly Gated Transmission

Introduction

• The Neuromuscular Junction Is a Well-Studied Example of Directly Gated Synaptic Transmission

• The Motor Neuron Excites the Muscle by Opening Ligand-Gated Ion Channels at the End-Plate

  • The End-Plate Potential Is Produced by Ionic Current Through Acetylcholine Receptor-Channels

  • The Ion Channel at the End-Plate Is Permeable to Both Sodium and Potassium

• The Current Through Single Acetylcholine Receptor-Channels Can Be Measured Using the Patch Clamp

  • Individual Receptor-Channels Conduct All-or-None Unitary Currents

  • Four Factors Determine the End-Plate Current

• The Molecular Properties of the Acetylcholine Receptor-Channel Are Known

• An Overall View

• Postscript: The End-Plate Current Can Be Calculated from an Equivalent Circuit

Communication between neurons in the brain relies mainly on chemical synapses. Much of our present understanding of the function of these synapses is based on studies of synaptic transmission at the nerve-muscle synapse, the junction between a motor neuron and a skeletal muscle fiber. This is the site where synaptic transmission was first studied and remains best understood. Moreover, the nerve-muscle synapse is the site of a number of inherited and acquired neurological diseases. Therefore, before we examine the complexities of synapses in the central nervous system, we will examine the basic features of chemical synaptic transmission at the nerve-muscle synapse.

The nerve-muscle synapse is an ideal site for study ing chemical signaling because it is relatively simple and accessible to experimentation. The muscle cell is large enough to accommodate the two or more micro electrodes needed to make electrical measurements. Also the muscle cell normally receives signals from just one presynaptic axon, in contrast to the convergent connections on central nerve cells. Most importantly, chemical signaling at the nerve-muscle synapse involves a relatively simple mechanism: Release of neurotransmitter from the presynaptic nerve directly opens a single type of ion channel in the postsynaptic membrane.

The Neuromuscular Junction Is a Well-Studied Example of Directly Gated Synaptic Transmission

The motor neuron innervates the muscle at a specialized region of the muscle membrane called the end-plate, where the motor axon loses its myelin sheath and splits into several fine branches. The ends of the fine branches form multiple expansions or varicosities, called synaptic boutons, from which the motor neuron releases its transmitter. Each bouton is positioned over a specialized region of the muscle membrane containing deep depressions, or junctional folds, which contain the transmitter receptors (Figure 9–1). The transmitter released by the motor axon terminal is acetylcholine (ACh) and the receptor on the muscle membrane is the nicotinic type of ACh receptor.¹