Protein Operated Channels

The muscarinic ACh receptors are formed from only a single subunit, which can bind to one ACh molecule. Unlike the nicotinic receptors, these receptors do not contain ion channels. The ion channels are separate proteins located at some distance from the muscarinic receptors. Binding of ACh (the ligand) to the mus-carinic receptor causes it to activate a complex of proteins in the cell membrane known as G-proteins—so named because their activity is influenced by guanosine nucleotides (GDP and GTP).

There are three G-protein subunits, designated alpha, beta, and gamma. In response to the binding of ACh to its receptor, the alpha subunit dissociates from the other two subunits, which stick together to form a beta-gamma complex. Depending on the specific case, either the alpha subunit or the beta-gamma complex then diffuses through the membrane until it binds to an ion channel, causing the channel to open (fig. 7.24). A short time later, the G-protein alpha subunit (or beta-gamma complex) dissociates

The Nervous System: Neurons and Synapses

Protein Alpha Subunit

G-protein subunit dissociates

Receptor

G-proteins

G-protein subunit dissociates

Receptor

G-proteins

G-protein binds to K+ channel, causing it to open

Plasma membrane

Plasma membrane

Protein Channels

G-protein binds to K+ channel, causing it to open

K+ channel

K+ channel

■ Figure 7.24 Muscarinic ACh receptors require the mediation of G-proteins. The figure depicts the effects of ACh on the pacemaker cells of the heart. Binding of ACh to its muscarinic receptor causes the beta-gamma subunits to dissociate from the alpha subunit. The beta-gamma complex of G-proteins then binds to a K+ channel, causing it to open. Outward diffusion of K+ results, slowing the heart rate.

Table 7.7 Steps in the Activation and Inactivation of G-Proteins

Step 1 The alpha, beta, and gamma G-proteins are joined together and bind to GDP before the arrival of the neurotransmitter.

Step 2 The ligand (neurotransmitter chemical) binds to its receptor in the membrane.

Step 3 GDP is released, and the alpha subunit of the G-proteins binds

GTP.

Step 4 This causes the dissociation of the alpha subunit from the beta-

gamma subunits.

Step 5 In different cases, either the alpha subunit, or the beta-gamma complex, can interact with membrane ion channels or membrane-bound enzymes.

Step 6 Deactivation is initiated by the hydrolysis of GTP to GDP by the alpha subunit.

Step 7 Bound to GDP again, the alpha subunit comes back together with the beta-gamma complex to reassemble the alpha-beta-gamma G-proteins.

from the channel and moves back to its previous position. This causes the ion channel to close. The steps of this process are summarized in table 7.7.

The binding of ACh to its muscarinic receptors indirectly affects the permeability of K+ channels. This can produce hyper-polarization in some organs (if the K+ channels are opened) and depolarization in other organs (if the K+ channels are closed). Specific examples should help to clarify this point.

Scientists have learned that it is the beta-gamma complex that binds to the K+ channels in the heart muscle cells and causes these channels to open (fig. 7.24). This leads to the diffusion of K+ out of the postsynaptic cell (because that is the direction of its concentration gradient). As a result, the cell becomes hyperpolar-

ized, producing an inhibitory postsynaptic potential (IPSP). Such an effect is produced in the heart, for example, when autonomic nerve fibers (part of the vagus nerve) synapse with pacemaker cells and slow the rate of beat. It should be noted that inhibition also occurs in the CNS in response to other neurotransmitters, but those IPSPs are produced by a different mechanism.

There are cases in which the alpha subunit is the effector, and examples where its effects are substantially different from the one shown in figure 7.24. In the smooth muscle cells of the stomach, the binding of ACh to its muscarinic receptors causes a different type of G-protein alpha subunit to dissociate and bind to the K+ channels. In this case, however, the binding of the G-protein subunit to the K+ channels causes the channels to close rather than to open. As a result, the outward diffusion of K+, which occurs at an ongoing rate in the resting cell, is reduced to below resting levels. Since the resting membrane potential is maintained by a balance between cations flowing into the cell and cations flowing out, a reduction in the outward flow of K+ produces a depolarization. This depolarization produced in these smooth muscle cells results in contractions of the stomach (see chapter 12).

Was this article helpful?

0 0
Essentials of Human Physiology

Essentials of Human Physiology

This ebook provides an introductory explanation of the workings of the human body, with an effort to draw connections between the body systems and explain their interdependencies. A framework for the book is homeostasis and how the body maintains balance within each system. This is intended as a first introduction to physiology for a college-level course.

Get My Free Ebook


Responses

  • ted
    How ach bind to g protein?
    8 years ago

Post a comment