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March 26, 2007
Lecture 30
NERVOUS SYSTEMS: COMMUNICATION
All multicellular animals, except for sponges, have a nervous system that is needed for
detection of the environment, coordination of locomotion and processing of internal cues.
There are some differences in the components of the nervous system but a striking
difference between animals is the organization of the nervous system (Fig. 48.2).
Simpler animals like hydra and echinoderms have nervous systems that are arranged in
nerve nets, which lack a central processing. More complex nervous systems have a
clustering of neurons in a brain near the anterior end, which constitute a central nervous
system (CNS), while the peripheral nervous system (PNS) consists of sensory and motor
neurons (Fig. 48.3). Thus the general flow of information in the nervous system is
specialized sensor detection of the environment or internal conditions are transmitted by
the sensory neurons to the CNS, where interneurons integrate and analyze the
information. Outputs leave the CNS through motor neurons to effect specific responses.
More complex organisms evolved peripheral segmental clusters of neurons called
ganglia, which permit faster processing and response through a reflex (Fig. 48.4).
The two main cellular components of the nervous system are neurons and glial or
supporting cells. The neuron consists of a cell body, which contains the nucleus,
numerous dendrites, which receives signals, and an axon, which transmits the signal to
another neuron or an effector cell like muscle (Fig. 48.5). Many vertebrate axons are
covered by a myelin sheath, which is a specialized structure formed by a glial Schwann
cell (Fig. 48.8). The site of communication between neurons or neuron and effector is
called the synapse. The presynaptic cell that transmitted the signal passes the
information through the synapse to a postsynaptic or receiving cell (Fig. 48.5). While
neurons are responsible for transmission of signal, the glial cells are responsible for the
integrity of the nervous system and proper functioning of the neurons. In mammalian
brains, glial cells outnumber neurons by at least 10-fold. Aside from Schwann cells
forming myelin sheaths, other glial cells are required for directing neuron circuitry and
forming the blood-brain barrier during development. Astrocytes in the CNS help
regulate extracellular conditions for neuron functions, but may also play a role in memory
and learning.
Transmission through a neuron is dependent on the membrane potential across the plasma
membrane. Like all cells the distribution of ions across the neuronal plasma membrane is
different between the extracellular fluid and the cytoplasm. Typical ionic gradients
across a mammalian neuronal membrane (Fig. 48.10) has a 10-fold greater concentration
of Na+ outside than inside and a 30-fold greater concentration of K+ inside than outside.
Typically anions like Cl- are more concentrated outside than inside due to the presence of
organic anions, such as nucleic acids. A contributing cause of this unequal distribution of
Na+ and K+ is the activity of the Na+, K+ ATPase. The typical resting neuron has a
resting membrane potential of about 70 mV inside negative (Fig. 48.9) because the
resting plasma membrane is more permeant to K+ than Na+. Thus more K+ exit the cell
than Na+ can enter and charge separation occurs or there is an excess of anions in the
cytoplasm. We can see that an ion gradient and selective membrane causes charge
separation and development of a membrane potential (Fig. 48.11a). The inside negative
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membrane potential will oppose the outward chemical gradient, such that an equilibrium
is reached and the K+ exit due to the chemical gradient is counterbalanced by the K+ entry
due to the inside negative electrical potential. The equilibrium potential for any given
chemical gradient can be determined by the Nernst equation, which is expressed as:
Eeq = 62 mV (log [ion]o/[ion]i) for a monovalent cation at T = 37oC and in the case of K+,
EK = 62 mV (log 5/150) = -92 mV . If we now consider the equilibrium potential for the
Na+ ionic gradient (Fig. 48.11), ENa = 62 mV (log 150/15) = +62 mV
Cell plasma membrane is mostly K+ permeant, but there is a slight Na+ permeability, such
that the cell resting potential is between -60 to -80 mV. Thus in a real cell where both K+
and Na+ are present, there is always a slight amount of K+ leaking out and of Na+ entering
the cell and the continuous activity of the Na+, K+ pump is required. Cells, especially
neurons have a variety of other membrane ion channels that are called gated ion
channels. Some of these are stretch-gated because the channels are opened or closed by
mechanical deformation. A second variety of gated ion channels are ligand-gated, which
open or close due to binding of a ligand, such as a neurotransmitter. Finally the gated
ion channels may be voltage-gated or opened or closed by a change in the membrane
potential. Often in cell signaling, a ligand-gated or stretch-gated channel opens to cause a
change in the membrane potential, which then activates voltage-gated channels.
Depending on the type of gated ion channel, the plasma membrane of a neuron can be
stimulated to become more negative or hyperpolarize (such as open more K+ or Clchannels) or stimulated to become more positive or depolarize (such as open Na+
channels). These membrane potential responses are called graded potentials because the
extent of membrane hyperpolarization or depolarization depends on the strength of the
stimulus. But most neurons have a threshold voltage where depolarization of the
membrane past the threshold voltage causes an action potential (Fig. 48.12). The action
potential is an all-or-none response due to sudden opening of voltage-gated Na+ channels
in the neuron plasma membrane. A more positive resting potential (membrane
depolarization) than the threshold voltage causes these Na+ channels to open and the
membrane becomes much more permeable to Na+ than K+ and the membrane potential
approaches the equilibrium potential for Na+. Most action potentials are very brief (a few
milliseconds) because most voltage-gated Na+ channels inactivate rapidly and voltagegated K+ channels open to cause the membrane permeability to become even more K+
selective and the action potential to undershoot the resting potential (Fig. 48.13) or
membrane hyperpolarization. These voltage-gated K+ channels also inactivate and the
neuron membrane returns back to its resting state.
For an action potential to be useful for transmission in an axon, the action potential has to
be conducted or propagated from one end of the axon to the opposite synapse. This
happens because the regional depolarization due to Na+ influx causes depolarization of
the neighboring region ahead of the action potential, such that threshold is reached and an
action potential is generated, which then depolarizes the next region, etc. (Fig. 48.14).
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The action potential travels towards the opposite synapse because the region behind the
action potential is repolarizing due to K+ efflux and the inactivation of the voltage-gated
Na+ channels (Fig. 48.14 #3). The conduction velocity of an action potential is greatly
increased by the presence of a myelin sheath around the axon. The myelin sheath is
periodically disrupted by a bare region or node of Ranvier (Fig. 48.15). Presence of the
myelin sheath prevents ion flow in or out of the cell, thus the axon can only generate an
action potential at the node of Ranvier. Thus an action potential must be sufficient to
depolarize the next node past the threshold voltage and generate an action potential. The
action potential jumps from one node to the next and this conduction is called saltatory.
There are two forms of synaptic transmission between the presynaptic and postsynaptic
cells. One limited type is an electrical synapse where the synapse consists of gap
junctions between the two cells. Since the gap junction allows passage of ions, the
electrical current of the presynaptic action potential directly flows into and depolarizes
the postsynaptic site to initiate an action potential in the postsynaptic neuron. Electrical
synapses are found associated with rapid, stereotypic responses, such as an escape reflex.
The majority of synaptic transmission is chemical synapses, where the action potential
causes opening of voltage-gated Ca2+ channels in the presynaptic neuron. The entry of
Ca2+ into the neuron causes the exocytosis of synaptic vesicles from the presynaptic site.
The vesicles contain neurotransmitter, which diffuses across the synaptic cleft or the
space between the presynaptic and postsynaptic cells (Fig. 48.17). The postsynaptic cell
membrane contains the appropriate ligand-gated ion channels, which act as receptors for
the neurotransmitter. Binding of the neurotransmitter to the ligand-gated ion channel
opens the channel and causes a postsynaptic potential that depends upon the type of
permeant ion. If the channel permits passage of Na+, then Na+ entry depolarizes the cell
and an excitatory postsynaptic potential (EPSP) is generated. If the channel permits
passage of Cl- or K+ only, then Cl- entry or K+ exit will hyperpolarize the cell and an
inhibitory postsynaptic potential (IPSP) is generated. The signal ends when the
neurotransmitter is destroyed by proteases in the synaptic cleft or when the receptors are
endocytosed. A postsynaptic neuron will often have numerous synaptic terminals and
thus the generation of an action potential in the postsynaptic cell is dependent on the
summation of postsynaptic potentials (Fig. 48.18).
Some ligand-gated ion channels are not regulated by the direct binding of a ligand to the
receptor ion channel, but by an indirect mechanism. In many cases of sensory perception
and memory the ligand activates a signaling cascade and the ion channels are regulated
by 2nd messengers. For example in taste bud receptor cells the binding of a ligand (ie:
sugar) to its receptor increases the level of cAMP, which activates protein kinase A and
phosphorylation of K+ channels, which closes these channels. Closure of the K+
channels, depolarizes the receptor cell membrane, thus opening voltage-gated Ca2+
channels, followed by Ca2+ influx and further neurotransmitter release (Fig. 49.14).
Other ion channels may be directly regulated by 2nd messengers, such as in olfaction.
The binding of odorant to its receptor triggers elevation of cAMP, which binds to Na+
and Ca2+ permeant ion channels. The entry of Na+ and Ca2+ depolarizes the olfactory
receptor cells and trigger action potentials (Fig. 49.15).