Human Physiology, 14th edition (2016)

188 Chapter 7

produce hyperpolarization in some organs (if the K^1 chan-

nels are opened) and depolarization in other organs (if the

K^1 channels are closed). Specific examples should help to

clarify this point.

Scientists have learned that it is the beta-gamma com-

plex that binds to the K^1 channels in the heart muscle cells

and causes these channels to open ( fig. 7.27 ). This leads to the

diffusion of K^1 out of the postsynaptic cell (because that is

the direction of its concentration gradient). As a result, the cell

becomes hyperpolarized, producing an inhibitory postsynap-

tic 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 pro-

duced 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 7.27. In the smooth muscle cells of the

stomach, the binding of ACh to its muscarinic receptors causes

alpha subunits to dissociate and bind to gated K^1 channels. In

this case, however, the binding of the G-protein subunit to the

gated K^1 channels causes them to close rather than to open. As

a result, the outward diffusion of K^1 , which occurs at an ongo-

ing rate in the resting cell, is reduced to below resting levels.

Because the resting membrane potential is maintained by a bal-

ance between cations flowing into the cell and cations flowing

out, a reduction in the outward flow of K^1 produces a depo-

larization. This depolarization produced in these smooth mus-

cle cells results in contractions of the stomach (see chapter 9,

fig. 9.11).

( fig. 7.27 ). A short time later, the G-protein alpha subunit (or
beta-gamma complex) dissociates from the channel and moves
back to its previous position. This causes the ion channel to
close (or open). The steps of this process are summarized in
table 7.6 and are illustrated in chapter 6 (see fig. 6.31).
The binding of ACh to its muscarinic receptors indi-
rectly affects the permeability of K^1 channels. This can

Figure 7.27 Muscarinic ACh receptors require the action 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^1 channel, causing it to open. Outward diffusion of K^1 results,
slowing the heart rate.

1. ACh binds
   to receptor
   2. G-protein
   subunit
   dissociates
   3. G-protein
   binds to K+
   channel,
   causing it
   to open

ACh

G-proteins K+ channel

Plasma membrane

K+

K+

Receptor

α

β

γ

β

γ

Table 7.6 | Steps in the Activation and
Inactivation of G-Proteins

Step 1 When the membrane receptor protein is not bound to

its regulatory molecule ligand, the alpha, beta, and

gamma G-protein subunits are aggregated together

and attached to the receptor; the alpha subunit

binds GDP.

Step 2 When the ligand (neurotransmitter or other regulatory

molecule) binds to the receptor, the alpha subunit

releases GDP and binds GTP; this allows the

alpha subunit to dissociate from the beta-gamma

subunits.

Step 3 Either the alpha subunit or the beta-gamma complex

moves through the membrane and binds to a

membrane effector protein (either an ion channel or

an enzyme).

Step 4 Deactivation of the effector protein is caused by the

alpha subunit hydrolyzing GTP to GDP.

Step 5 This allows the subunits to again reaggregate and

bind to the unstimulated receptor protein (which is

no longer bound to its regulatory molecule ligand).