Download Lecture 1 Basics of neurons and signaling

Introduction to Neurobiology
Dauphin Island Sea Lab
July 20-August 8, 2015
Animal cells and their components 1
Nervous systems are made up of
neurons and glia. Both have the same
components as other cells including
intracellular structures called organelles.
Nucleus: The nucleus has two major functions:
it stores the cell's hereditary material, or DNA,
and it coordinates growth, intermediary
metabolism, protein synthesis, and
reproduction (cell division).
Centrioles: Centrioles are self-replicating
organelles made up of nine bundles of
microtubules and are found only in animal cells.
They appear to help in organizing cell division,
but aren't essential to the process.
Endoplasmic Reticulum: The endoplasmic
reticulum is a network of sacs that
manufactures, processes, and transports
chemical compounds for use inside and outside
of the cell. It is connected to the double-layered
nuclear envelope, providing
a connection between the nucleus and the
cytoplasm.
http://micro.magnet.fsu.edu/cells/animalcell.html
Animal cells and their components 2
Endosomes and Endocytosis: Endosomes are
membrane-bound vesicles, formed via
processes collectively known as endocytosis,
and are found in the cytoplasm of virtually
every animal cell. It involves the invagination
(folding inward) of a cell's plasma membrane
to surround macromolecules or other matter
in the extracellular fluid.
Ribosomes: All living cells contain ribosomes
which create proteins from amino acids
through the action of mRNA and tRNA. The
amino acids are attached to transfer RNA
(tRNA) molecules, which enter one part of
the ribosome and bind to the messenger RNA
sequence. The attached amino acids are then
joined together by another part of the
ribosome. The ribosome moves along the
mRNA, "reading" its sequence and producing
a chain of amino acids.
Intermediate Filaments: These are fibrous
Golgi Apparatus: The Golgi apparatus
proteins that play roles as both structural
modifies proteins and fats synthesized in the and functional elements of the cytoskeleton.
endoplasmic reticulum and prepares them
They function as tension-bearing elements to
for transport within the cell or exocytosis.
help maintain cell shape and rigidity.
Animal cells and their components 3
Microfilaments: Rods made of globular
proteins called actin (6 nm in diameter). They
are primarily structural in function and are an
important component of the cytoskeleton.
Microtubules: Straight, hollow cylinders (25nm
diameter) found throughout the cytoplasm of
all eukaryotic cells and their functions range
from transport to structural support.
Lysosomes: Their main function is digestion.
The lysosomes break down cellular waste
products and debris from outside the cell into
simple compounds, which are transferred to
the cytoplasm as new cell-building materials.
Cilia and Flagella: Cilia and flagella are
essential for the locomotion of some types of
individual organisms. In multicellular
organisms, cilia function to move fluid or
materials past an immobile cell as well as
moving a cell or group of cells.
Mitochondria: Mitochondria are oblong
shaped organelles that are the main power
generators, converting oxygen and nutrients
into energy.
The cell membrane
Plasma Membrane: All living cells have a plasma membrane that encloses their contents.
It protects the contents, and also regulates the passage of molecules in and out of the
cells. The plasma membrane is a lipid bilayer, with the nonpolar hydrophobic tails
pointing toward the inside of the membrane and the polar hydrophilic heads forming the
inner and outer surfaces of the membrane.
The membrane is very selective about what it allows to pass through; this characteristic
is referred to as "selective permeability." For example, it allows oxygen and nutrients to
enter the cell while keeping toxins and waste products out. Only small, uncharged polar
molecules can pass freely across the membrane. Other molecules need the help of
membrane proteins to get across. Proteins and cholesterol molecules are scattered
throughout the flexible phospholipid membrane.
The cell membrane
There are a variety of membrane proteins that serve various functions: Some proteins
attach loosely to the inner or outer surface of the plasma membrane. Integral proteins
extend across the membrane, from inside to outside. Proteins are scattered throughout
the flexible matrix of phospholipid molecules, somewhat like icebergs floating in the
ocean, and this is termed the fluid mosaic model of the cell membrane.
Channel proteins: Proteins that provide passageways through the membranes for certain
hydrophilic or water-soluble substances such as polar and charged molecules. No energy
is used during transport, hence this type of movement is called facilitated diffusion.
Transport proteins: Proteins that spend energy (ATP) to transfer materials across the
membrane. When energy is used to provide passageway for materials, the process is
called active transport.
Adhesion proteins: Proteins that attach cells to neighboring cells or provide anchors for
the internal filaments and tubules that give stability to the cell.
Receptor proteins: Proteins that initiate specific cell responses once hormones or other
trigger molecules bind to them
Back to mitochondria: They are 0.5 to 1.0 um in diameter. They have their own
DNA and in humans they are inherited from the mother. They can divide, change
shape and ruse with other mitochondria.
Cytoskeleton
The cytoskeleton of cells
is comprised of actin filaments,
Intermediate filaments, and
microtubules. The cytoskeleton
helps to maintain the shape of
cells, but is very dynamic, and
cytoskeletal remodeling is the
reason that cells can migrate. It is
also critical in neuronal
development.
Introduction: Why are cells of the nervous system not
something else?
Genes encode proteins. Each human cell has roughly 20-25,000 protein-encoding
genes in its nucleus. But each cell uses only a subset of those genes and they
turn on and off as the cell progresses through its life. What differentiates one
cell type from another is differential gene expression. That is, what genes are
expressed, what genes are not expressed and when all of this happens. More of
the genome is expressed in the nervous system than in any other organ system of
the body.
In addition to the protein-encoding region of the gene, there are regulatory
sequences called promoters and enhancers, that are necessary for controlling
when and in what cells a gene is transcribed. A promoter is the site where RNA
polymerase binds to the DNA to initiate transcription of a gene. An enhancer is a
DNA sequence that that controls the efficiency and rate of transcription of a
specific promoter.
Other proteins, called transcription factors, bind to the promoter or enhancer
regions and interact to activate or repress the transcription of a particular gene.
Transcription factors often directly regulate not just one but often a large number
of downstream target genes.
Examples of transcription factors: Microphthalmia (MITF)
The microphthalmia transcription factor is active in the ear and pigment forming
cells of the eye and skin. Humans heterozygous for a mutation in the gene that
encodes MITF are deaf, have small eyes and multi- colored irises, and a white
forelock in their hair. This is called Waardenburg syndrome.
Pax 6: This transcription factor is needed for the development of the mammalian
eye, nervous system, and pancreas. Homozygous Pax 6 mutant rats and mice
lack eyes and a nose. People who are heterozygous for a mutant form of Pax 6
or who lack one copy of the gene have little or no iris (aniridia).
Examples of the rich variety of nerve cell morphologies found in humans.
Nervous systems are made up of neurons and glia: there are an
estimated 100,000,000,000 neurons in the brain
Clusters of functionally related
neurons in the brain form nuclei.
Hence the neurons of the lateral
geniculate nucleus receive input
from retinal ganglion cells. In
animals without backbones,
these clusters are often clled
ganglia.
Examples of the rich variety of nerve cell morphologies found in humans.
Examples of the rich variety of nerve cell morphologies found in humans.
Glia: There are an estimated
100,000,000,000 neurons in the
brain, and there are many times
that number of another cell type,
glia. Glia are also very complex
but for today, there are 3 basic
types. Glia have a variety of
important functions. They help to
form the blood-brain barrier, they
serve to provide myelin sheaths
around axons that increase the
speed of action potential
conduction, they play a nutritive
role, and they help to recycle
neurotransmitters.
Some glia also express
neurotransmitter receptors and
can respond to transmitters
released from neurons. Some
glia can also release
neurotransmitters and other
neuroactive substances
themselves that affect the
activity of neurons.
Blood brain barrier
This image shows the blood
vessels in a human from just
above the knees to the head.
Blood vessels in the brain are
different than in other parts of
the body. This was first
observed in the mid 1800s by a
bacteriologist named Paul
Ehrlich and his student, Edwin
Goldman.
The ability of substances to move from
the vasculature into the brain is
controlled by the blood brain barrier.
It is the result of tight junctions
between neighboring vascular
endothelial cells. In addition, the
outside of the capillary is surrounded
by the end feet of astrocytes. So
molecules that move from the blood
into the brain have to pass through the
endothelial cells and traverse the
astrocyte end feet.
Electrical signals
Terms in electrophysiology
Ion: An atom or molecule in which the total number of electrons is not equal to
the total number of protons, giving it a net positive or negative electrical charge.
Examples include Na+, K+, Cl-, and Ca2+.
Current: A flow of electric charge through a medium. For this course, we will
often use this in the context of the charge is carried by ions in a solution. Units:
amperes
Voltage: the voltage between two points is the total energy required to move a
small electric charge along that path. Units: volts
Resistance: The opposition to the passage of an electric current. Units: ohms
Ohm’s Law: V=IR
Voltage=current x resistance
Neuronal signals
2.2 Recording passive and active electrical signals in a nerve cell. (Part 1)
2.2 Recording passive and active electrical signals in a nerve cell. (Part 2)
2.4 Electrochemical equilibrium. (Part 1)
Membrane potentials
The equilibrium potential (sometimes called the Nernst potential) can be predicted
by a simple equation-the Nernst equation. (Walter Nernst, electrochemist; won the
Nobel prize in 1920)
Ex= RT/ZF ln([X]o/[X]i
If z=1 (Na+, K+) then Ex=58 log [X]o/[X]I
• R (Gas Constant) = 8.314472 (J/K·mol)
• T (Absolute Temperature) = t °C + 273.15 (°K)
• F (Faraday's Constant) = 9.6485309×104 (C/mol)
2.4 Electrochemical equilibrium. (Part 2)
2.5 Membrane potential influences ion fluxes. (Part 1)
2.5 Membrane potential influences ion fluxes. (Part 2)
Box A The Remarkable Giant Nerve Cells of a Squid
2.7 Evidence that the resting potential is determined by K+ concentration gradient. (Part 1)
2.7 Evidence that the resting potential is determined by K+ concentration gradient. (Part 2)
The problem is that in real cells there are several ions in solution, not just one.
These include Na+, K+, Cl-, etc. The Nernst equation is not applicable in these cases.
There is an equation that allows us to calculate the resting membrane
potential of a neuron.
It’s called the Goldman Hodgkin Katz equation, or GHK for short.
Things to discuss:
• Permeability
• Cl• What about Ca2+
R (Gas Constant) = 8.314472 (J/K·mol)
T (Absolute Temperature) = t °C + 273.15 (°K)
F (Faraday's Constant) = 9.6485309×104 (C/mol)
2.6 Resting and action potentials entail permeabilities to different ions.
2.8 The role of sodium in the generation of an action potential. (Part 1)
2.8 The role of sodium in the generation of an action potential. (Part 2)
Box B Action Potential Form and Nomenclature
2.3 Ion transporters and channels are responsible for ionic movements across membranes.