Chapter 4 – Excitability ad Chemical Signaling in Nerve Cells
- All thoughts, emotions and behaviours come about because of biochemical and electrochemical
processes that take place in specialized cells in the nervous system called neurons.
- Drugs that affect these psychological variables do so because they alter these biochemical and
- The nervous system is divided into two systems:
o The Central Nervous System (CNS) which is composed of the brain, and the spinal cord
o The Peripheral Nervous System (PNS) which is made up of all neurons outside the brain
and spinal cord
- Neurons are also mixed in with numerous other nonneuronal cellular elements called:
o Glial cells which ensheath synaptic connections between neurons and are required for
synapse formation and maintenance
o Oligodendrocytes which wrap layers of myelin membrane around axons to insulate
them for impulse conduction, which serve important metabolic and supportive
- It has been estimated that the human nervous system contains approximately 85 billion
- Neurons act to transducer information about their physical and chemical environments, which
means that they convert one form of energy into another form of energy or one type of signal
into another type of signal. In addition, neurons transmit information, typically by generating
electrical changes in one part of the cell, conducting these electrical changes to distant parts of
the cell, then releasing chemical signals onto the neighbouring neuron.
o They are chemically active, releasing signaling molecules known as neurotransmitters.
- Each neuron has numerous excitatory and inhibitory inputs or synapses, which regulate the
frequency of action potentials produced by them. - The large arrows indicate the most common direction of information flow.
- The main body of the neuron is called the soma, parts of which serve integrative functions in the
communication of information.
- Extensions from the soma are termed dendrites and axons. The enlarged region where the axon
emerges from the soma is called the Axon Hillock.
- Normally there are many dendrites extending from the soma, which serve as receivers for
information from other neuron, and one axon, which serves as the pathway over which signals
pass from the some to other neurons.
- Dendrites tend to be relatively short, but axons can be quite long. Many axons have a coating
called the myelin sheath, which is analogous to the insulation on a wire. Gaps in the myelin
sheath where the axon comes into direct contact with the extracellular fluid, are called the
nodes of Ranvier. The presence of these gaps allow for an increase in the rate of conduction
down the axon. Near its end, the axon branches and at the tip of each branch is an enlargement
called a terminal/varicosities. Chemicals found within the axon terminal can be released into an
exceedingly small gap between the neurons, called a synaptic cleft, allowing the neuron to
affect excitability of adjacent neurons. The point of functional connection between neurons is
called a synapse and it consists of the pre-synaptic membrane of the axon terminal, the synaptic
cleft and the post-synaptic membrane of the “target” neuron.
Electrical Excitability of Neurons: The Resting Membrane Potential
- Neurons are electrically active. Under baseline conditions, each neuron is said to be polarized;
that is, they have a voltage difference between the inside and the outside of the cell that is
known as the resting membrane potential. In neurons, this difference is approximately 70mV.
Because the inside of the cell membrane is negative, this voltage is referred to as -70mV. The
resting potential of individual neurons varies between -60 and -90mV. This electrical potential or
charge is largely powered by sodium ions (Na ). +
- Things that generate the resting potential:
o The electrical characteristics of ions
o The physical forces that drive the movements of ions
o The characteristics of the nerve cell membrane, including both the lipid and protein
- Several ions that need to be considered:
o Sodium (Na )+
o Potassium (K )
o Chloride (Cl) There are also large negatively charged groups on protein molecules which
tend to be present in higher concentrations inside the membrane
o Calcium (Ca )+
- Any positive ion is called a cation, while a negative is called an anion.
- In addition, there are two main physical forced that we need to consider, which drive the
movement of ions and other molecules. o Movement along a concentration gradient refers to the fact that molecules move from
an area of high concentration to an area of low concentration.
o An electrical gradient refers to ions being driven by electrical forces because like
charges repel and opposites attract.
- Characteristics of the neural membrane:
o As reviewed in chapter 3, the nerve cell membrane consists of a phospholipid bilayer
with imbedded proteins. The lipid portion of the bilayer acts as a barrier to the
movement of ions or polar substances.
o The protein components can include :
Enzymes – biological catalysts that promote biochemical reactions including
neurotransmitter synthesis and metabolism.
Receptors – bind to neurotransmitters essentially acting as the initial detection
device for the presence of a transmitter.
Channels – proteins that act as gates that can be opened or closed. When
opened the channels allow for the passage of ions through the membrane.
Channels are defined in terms of what ions they let though. Cation channels,
anion channels, Na channels, K channels, CL channels and Ca channels, as
well as defined by their gating mechanism (what opens and closes them).
Transporters – act as pumps that move substances across the membrane.
o Each of the proteins can serve as a substrate for drug action.
- Under baseline or resting conditions:
o Cl and K channels are mostly open
o Na channels are virtually all closed
o Na /K pump actively transports some K into the cell but transports more Na out of it.
o These conditions lead to the generation of the resting membrane potential. It is
negative on the inside because positively charged Na ions are pumped out, and these
ions are not allowed back in because the Na channels are closed. Thus, under the
resting or baseline conditions, the membrane is impermeable to sodium ions. This
established the inside of the membrane is relatively negative and the outside is
o With more Na+ ions on the outside, the two forces that impinge upon the movement of
ions are aligned and have the potential to act upon Na+ in the same direction. If the
membrane were to suddenly become permeable to Na+, the sodium ions would rush
into the cell driven by both the concentration gradient force and the electrical gradient
force. Thus the resting or baseline condition represents an electrically unstable state
because anything that increases the permeability to Na+ would discharge the capacitor
(would allow sodium to flow through the membrane and make the inside of the
membrane more positive).
o This is how neurons change from the polarized resting or baseline state to become
excited or depolarized.
Electrical Excitability of Neurons: Excitation, inhibition and the Action Potential - Electrical conditions across the membrane can be recorded by electrodes, and when this is
done, a variety of voltage or current changes can be measured.
- Three types of electrical phenomena are commonly recorded from nerve cells.
o Excitatory postsynaptic potentials (EPSPs) is a small transient change in the positive
direction ie moves in a positive direction then returns to baseline.
o Inhibitory postsynaptic potentials (IPSPs) is a small change in the negative direction ie
the cell becomes more negative/hyperpolarized).
o Action potentials (spikes/neuronal firing) is a rapid and dramatic movement in the
positive direction, followed by a rapid restoration of the resting potential.
o The term potential here refers to a voltage change, post synaptic refers to the
convention that these are generally recorded from the postsynaptic membrane.
- We say that EPSPs and IPSPs are propagated in a graded decremental fashion. They originate at
one point and move outward in all directions across the surface of the membrane. They are said
to be graded because they can vary in size, depending upon the magnitude of the stimulus, and
decremental because they diminish in size as they travel out from the original point of
- EPSPs and IPSPs convey information about the magnitude of the chemical signal that a neuron is
receiving. They are analogous to the ripples that occur when we throw a stone into a pond.
- In contrast, Action Potentials are not graded or decremental. When the level of excitation is
great enough to cross the threshold, an action potential is triggered and action potentials are
considered to be all or none. When they occur, they typically maintain their size as they travel
along the axonal membrane. Because they do not generally convey information based upon
their size, action potentials encode information in terms of their frequency and overall pattern
- Once generated, action potentials then travel down the axon, and in some cases this can be a
very long distance. The speed of the action potential is related to two main factors:
o The diameter of the axon (larger diameters conduct more rapidly)
o Whether or not it is myelinated (myelinated conduct more rapidly)
- Mechanisms that produce EPSPs and IPSPs are:
o Ones that lead to excitation
GLU is the most common excitatory transmitter. It induces excitation by binding
to a receptor known as N-methyl D-aspartate (NMDA) receptor. This receptor is
linked to a cation channel. When GLU molecules bind to the binding site, it
instigates the opening of the cation channel; positive ions flow through, and
because one of the ions that can pass through is Na+, this represents an
increase in permeability to Na+. The inward flow results in the inside of the
membrane moving in the positive direction which is recorded as an EPSP.
o Ones that lead to inhibition
GABA is the most common inhibitory transmitter. It can induce inhibition by
binding to a receptor subtype known as GABAa. The GABAa receptor is linked to
a Cl- channels and therefore when GABA molecules bind to the binding site, it
instigates an opening of this chemically gated Cl- channel. As a result there is an inward flow which moves the voltage in the negative direction, and the change
is recorded as an IPSP.
o It is the different channels being opened that leads to either excitation or inhibition in
each of these cases.
- Action potentials are generated by a different mechanism that EPSPs and IPSPs. Under
physiological conditions, action potentials are most frequently generated at the initial portion of
the axon (the Axon Hillock).
- Consider an action potential having two parts:
o An ascending limb – when the voltage shoots up in the positive direction
It is instigated because of the opening of voltage-gated Na+ channels. An initial
voltage change triggers the opening of these channels, which leads Na+ ions to
go into the neuron, which leads to the membrane potential on the inside to
shoot up in the positive direction. Meanwhile the membrane depolarization
induces the opening of voltage-gated K+ channels.
o A descending limb – wh