Passage V

Introduction

A skeletal neuromuscular junction (NMJ; see the figure) is composed of a synaptic terminal (a tip of an axon of a neuron), a motor end plate (a depression in the plasma membrane of a muscle fiber), and a synaptic cleft (the region between these 2 structures). The synaptic terminal contains synaptic vesicles: structures that contain the neurotransmitter acetylcholine (ACh). When the neuron fires, synaptic vesicles fuse with the neuron's plasma membrane and release ACh into the synaptic cleft. ACh then diffuses across the synaptic cleft and binds to ACh receptors (membrane proteins produced by the muscle fiber) in the motor end plate. If this binding does not occur, the muscle fiber cannot contract.

If a person ingests botulin (a toxin), it enters the bloodstream, diffuses into NMJ synaptic clefts, and disrupts the contraction of the muscle fibers associated with these NMJs. Four hypotheses propose mechanisms for the disruption of function at an NMJ.

Hypothesis 1

Botulin is absorbed from the synaptic cleft by the synaptic terminal. Botulin then binds to and breaks down the neuron's docking proteins (proteins required for the fusion of synaptic vesicles with the neuron's plasma membrane). Because the vesicles cannot fuse with the plasma membrane, they cannot release ACh into the synaptic cleft. Thus, ACh does not bind to the ACh receptors. Therefore, the muscle fiber cannot contract.

Hypothesis 2

Botulin remains in the synaptic cleft, where it binds to and breaks down ACh before the ACh can diffuse across the synaptic cleft and bind to the ACh receptors. Therefore, the muscle fiber cann't contract.

Hypothesis 3

Botulin remains in the synaptic cleft, where it binds to and irreversibly blocks the ACh receptors. As a result, ACh cannot bind to the ACh receptors. Therefore, the muscle fiber cannot contract.

Hypothesis 4

Botulin is absorbed from the synaptic cleft by the muscle fiber. Botulin then binds to and breaks down myosin, a protein that is an essential component of the contractile apparatus of a muscle fiber. As a result of this breakdown, the muscle fiber cannot contract.