Effect of Acetylcholine on the Muscle Cell

The goal of synaptic transmission at the neuromuscular junction is to cause the muscle cell to contract. Acetylcholine released from the synaptic terminal accomplishes this goal by depolarizing the muscle cell. Because muscle cells are excitable cells like neurons, this depolarization will set in motion an all-or-none, propagating action potential if the depolarization exceeds threshold. The coupling between the muscle action potential and contraction will be the subject of Chapter 10. This section will discuss the effect of ACh on the muscle cell membrane, leading to depolarization.

The region of muscle membrane where synaptic contact is made is called the end-plate region, and it possesses special characteristics. In particular, the end-plate membrane is rich in a transmembrane protein that acts as an ion channel. Unlike the voltage-dependent channels discussed in Chapter 6, however, this channel is little affected by membrane potential. Instead, this channel is sensitive to ACh: it opens when it binds ACh. Thus, ACh released from the

1. Presynaptic action potential

2. Depolarization of synaptic terminal

3. Voltage-sensitive calcium channels open v

4. Calcium enters synaptic terminal

5. Release of chemical neurotransmitter

Figure 8-4 Schematic representation of the behavior of the AChsensitive channel in the end-plate membrane. The binding of two molecules of ACh to sites on the channel opens the gate, allowing sodium and potassium ions to flow through the channel. (Animation available at www.blackwellscience.com)

Figure 8-4 Schematic representation of the behavior of the AChsensitive channel in the end-plate membrane. The binding of two molecules of ACh to sites on the channel opens the gate, allowing sodium and potassium ions to flow through the channel. (Animation available at www.blackwellscience.com)

synaptic terminal diffuses across the synaptic cleft to the muscle membrane, where it combines with specific receptor sites associated with the ion channel. As shown schematically in Figure 8-4, the gate on the channel is closed in the absence of ACh. When the receptor sites are occupied, however, the gate opens, and the channel allows ions across the membrane. Two ACh molecules must bind to the channel in order for the gate to open (Figure 8-4). The ACh-binding site is highly specific; only ACh or a small number of structurally related compounds can bind to the site and cause the channel to open.

The ACh-activated channel of the muscle end-plate allows both sodium and potassium to cross the membrane about equally well. Thus, when ACh is present, the membrane permeability to both sodium and potassium increases. How can such a permeability increase produce a depolarization of the muscle cell? To see this, consider the situation diagrammed in Figure 8-5. Recall from Chapter 5 that membrane potential depends on the relative sodium and potassium permeabilities of the membrane (the Goldman equation). For the cell of Figure 8-5, pNa/pK is 0.02 at rest and Em would be about -74 mV, assuming typical ECF and iCf (Table 2-1). In the presence of ACh, however, pNa and pK increase by equal amounts; pNa/pK increases to 0.51 and Em depolarizes to about -17 mV.

The ACh-activated channels are packed densely in the end-plate region of the muscle, as illustrated in Figure 8-6a. The membrane is studded with ring-shaped particles that are found only at the region of synaptic contact. These particles have been biochemically isolated from the postsynaptic membrane and identified as the ACh-binding receptor molecule and its associated channel. The isolated receptor/channel complex can be inserted into artificial membranes, where they retain their function and their appearance through the electron microscope (Figure 8-6b). The hole in the middle of each particle is probably the aqueous pore through which the sodium and potassium ions cross the membrane.

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