The Nervous System 185Chemically Regulated Channels
The binding of a neurotransmitter to its receptor protein
can cause the opening of ion channels through two different
mechanisms. These two mechanisms can be illustrated by the
actions of ACh on the nicotinic and muscarinic subtypes of the
ACh receptors.Ligand-Gated Channels
As previously mentioned, a neurotransmitter molecule is the
ligand that binds to its specific receptor protein. For ion chan-
nels that are “ligand-gated,” the receptor protein is also an ion
channel; these are two functions of the same protein. Part of this
protein has extracellular sites that bind to the neurotransmitter
ligands, while part of the protein spans the plasma membrane
and has a central ion channel. For example, there is a family
of related ligand-gated channels that consist of five polypep-
tide chains surrounding an ion channel. This receptor family
includes the nicotinic ACh receptors discussed here, as well as
different receptors for the neurotransmitters serotonin, GABA,
and glycine (discussed later in this chapter). Although there are
important differences among these ligand-gated channels, all
members of this family function in a similar way: when the neu-
rotransmitter ligand binds to its membrane receptor, a central
ion channel opens through the same receptor/channel protein.
The nicotinic ACh receptor can serve as an example of
ligand-gated channels. Two of its five polypeptide subunits
contain ACh-binding sites, and the channel opens when both
sites bind to ACh ( fig. 7.26 ). The opening of this channel per-
mits the simultaneous diffusion of Na^1 into and K^1 out of
the postsynaptic cell. The effects of the inward flow of Na^1
predominate because of its steeper electrochemical gradient.
This produces the depolarization of an excitatory postsynaptic
potential (EPSP).
Although the inward diffusion of Na^1 predominates in an
EPSP, the simultaneous outward diffusion of K^1 prevents the
depolarization from overshooting 0 mV. Therefore, the mem-
brane polarity does not reverse in an EPSP as it does in an
action potential. (Remember that action potentials are produced
by separate voltage-gated channels for Na^1 and K^1 , where the
channel for K^1 opens only after the Na^1 channel has closed.)
A comparison of EPSPs and action potentials is provided in
table 7.4. Action potentials occur in axons, where the voltage-
gated channels are located, whereas EPSPs occur in the den-
drites and cell body. Unlike action potentials, EPSPs have no
threshold; the ACh released from a single synaptic vesicle pro-
duces a tiny depolarization of the postsynaptic membrane. When
more vesicles are stimulated to release their ACh, the depolariza-
tion is correspondingly greater. EPSPs are therefore graded in
magnitude, unlike all-or-none action potentials. Because EPSPs
can be graded and have no refractory period, they are capable
of summation. That is, the depolarizations of several different
EPSPs can be added together. Action potentials are prevented
from summating by their all-or-none nature and by their refrac-
tory periods.Acetylcholine (ACh) is used as an excitatory neurotransmitter
by some neurons in the CNS and by somatic motor neurons at
the neuromuscular junction. At autonomic nerve endings, ACh
may be either excitatory or inhibitory, depending on the organ
involved.
Postsynaptic cells can have varying responses to the same
chemical partly because different postsynaptic cells have dif-
ferent subtypes of ACh receptors. These receptor subtypes can
be specifically stimulated by particular toxins and are named
for these toxins. The stimulatory effect of ACh on skeletal
muscle cells is produced by the binding of ACh to nicotinic
ACh receptors, so named because they can also be activated
by nicotine. Effects of ACh on other cells occur when ACh
binds to muscarinic ACh receptors, so named because these
effects can also be produced by muscarine (a drug derived
from certain poisonous mushrooms).
An overview of the distribution of the two types of ACh
receptors demonstrates that this terminology and its associ-
ated concepts will be important in understanding the physiol-
ogy of different body systems. The two types of cholinergic
receptors (receptors for ACh) are explained in more detail in
chapter 9 (see fig. 9.11).
- Nicotinic ACh receptors. These are found in specific
regions of the brain (chapter 8), in autonomic ganglia
(chapter 9), and in skeletal muscle fibers (chapter 12). The
release of ACh from somatic motor neurons and its subse-
quent binding to nicotinic receptors, for example, stimu-
lates skeletal muscle contraction. - Muscarinic ACh receptors. These are found in the plasma
membrane of smooth muscle cells, cardiac muscle cells,
and the cells of particular glands (chapter 9). Thus, the
activation of muscarinic ACh receptors by ACh released
from autonomic axons is required for the regulation of
the cardio vascular system (chapter 14), digestive system
(chapter 18), and others. Muscarinic ACh receptors are
also found in the brain.
Drugs that bind to and thereby activate receptor pro-
teins are called agonists, and drugs that bind to and thereby
reduce the activity of receptor proteins are antagonists.
For example, muscarine (from the poisonous Amanita mus-
caria mushroom) is an agonist of muscarinic ACh receptors,
whereas atropine —a drug derived from Atropa belladonna,
a member of the deadly nightshade family—is an antagonist
of muscarinic receptors. Nicotine (from tobacco plants) is
an agonist for nicotinic ACh receptors; antagonists include
a -bungarotoxin (from krait snake venom) and curare (see
table 7.5 ).
10. Describe the action and significance of
acetylcholinesterase.- Compare EPSPs and action potentials, identify
where each is produced in a neuron, and explain
how action potentials can be stimulated by EPSPs.