Mol Neurophar, Ch 2

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nerve cells in all animals are basically the same in terms of

Back 1

cell biology

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"what is different during ontogeny and phylogeny?

Ontogeny is the origin and the development of an organism

phylogen: the history of the evolution of a species or group"

Back 2

arrangement of nerve cells into functional circuits: the achitecture of the nervous system

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neuron doctrine

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each neuron is an individual entity, the basic unit of neural circitry

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hydra's body wall (3 layers)

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"ectoderm: outer layer (contacting the external enviroment) -

mesoderm: middle layer

endoderm: layer facing body's cavity: promotes digestion and waste elimination


"

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neurons probably differentiated initially from the

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"ectoderm

first to evolve were probably sensory neurons"

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afferent neuron

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convey information from tissues and organs into the central nervous system and are sometimes also called sensory neurons.

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Efferent neurons

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transmit signals from the central nervous system to the effector cells and are sometimes called motor neurons

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effector cell

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The muscle, gland or organ cell capable of responding to a stimulus at the terminal end of an efferent neuron or motor neuron.

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sensory neurons provide 4 major selective advantages in evolution

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"increased stimulus sensitivity

faster effector cell responses

stronger behavioral responses because multiple effectors cells are influenced

sensory neurons responding to different stimulus modalities can be distributed strategically in different body regions"

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what shape are sensory neurons?

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"bipolar

this is fundamentally important (in early dev all have bipolar shape - but over course of evolution they have become specialized depending on function)"

Front 11

functional polarity theory

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information normally flows in one direction through most neurons, and thus through neural circuits - from dentrites to cell body, the input or receptive part of the neuron, to a single axon, the output or effector part.

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most neurons have 2 classes of processes

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"one or more dedrites detecting inputs

a single axon conducting an output that can influence multiple cells through branching or collateralizaiton"

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collateralization

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is the growth of a blood vessel or several blood vessels that serve the same end organ or vascular bed as another blood vessel that cannot adequately supply that end organ or vascular bed sufficiently

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for each neurotransmitter there are _______________ receptors

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multiple

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initial binding of a drug to its target (receptor) is only the beginning of a ___________ _______________ that affects the behavior of cells and ultimately complex circuits

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signalling cascade

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Allosteric regulation

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"allosteric regulation is the regulation of an enzyme or other protein by binding an effector molecule at the protein's allosteric site (that is, a site other than the protein's active site).

Effectors that enhance the protein's activity are referred to as allosteric activators, whereas those that decrease the protein's activity are called allosteric inhibitors.

Allostery ""solid (object)"": (1) in reference to the fact that the regulatory site of an allosteric protein is physically distinct from its active site. (2) designating a function of an enzyme in which the structure and activity of the enzyme are modified by the binding of a metabolic molecule

Allosteric regulations are a natural example of control loops, such as feedback from downstream products or feedforward from upstream substrates.

Long-range allostery is especially important in cell signaling."

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effector (molecule)

Back 17

"effector is a molecule (originally referring to small molecules but now encompassing any regulatory molecule, including proteins) that binds to a protein and thereby alters the activity of that protein.

A modulator molecule binds to a regulatory site during allosteric modulation and allosterically modulates the shape of the protein."

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The _______________ and major ______________ ______________ in the cell body of neurons synthesize and process proteins, which are subsequently transported to their appropriate locations within the neurons

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"nucleus

cytoplasmic organelles"

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the axon . . . .

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"transports molecules

conducts AP to the presynaptic terminals to initiate communication with other neurons (which occurs at synapses)"

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_____________ serves as the primary structure for the reception of synaptic contacts from other neurons

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dendrites

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cytoskeleton

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"the inner scaffold of a neuron formed by a system of interconnected protein filaments called microtubules, intermediate filaments and actin filaments

plays a key role in the structure of neurons and in the transport of various proteins and organelles from the cell body to axonal and dendritic processes"

Front 22

Na+/K+ pump helps to . . .

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maintain appropriate ionic gradients across the membrane

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____________ channels are the targets of many important drugs including local anesthetics and some antiseizure meds

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sodium

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generation of AP relies on the activities of . . .

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"voltage-dependant ion channels

highly specific ions (K+, Na+, or Ca++) across neuronal membranes in response to changes in neuronal membrane potential"

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3 general classes of potassium channels:

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"voltage-gated potassium channels

calcium-activated potassium channels

inward rectifiers"

Front 26

5 major classes of voltage-dependant calcium channels

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"L-type

N-type

T-type

P/Q-type

R-type"

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entry of calcium into neurons through voltage-dependant calcium channels are important for:

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"NT release

and activation of intracellular signaling cascades"

Front 28

L-type calcium channel blockers are used to treat

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hypertension & ischemic heart disease

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mutations in ion channels can cause

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"several neurological disorders

including certain inherited neuromuscular disorders"

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Purkinje cells

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"a class of GABAergic neurons located in the cerebellar cortex

some of the largest cells in the brain

found w/in the Purkinje layer in the cerebellum

Purkinje cells are affected in a variety of diseases ranging from toxic exposure (alchohol) to autoimmune diseases to genetic mutations"

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the ___________ is the critical cell type for communication in neural networks, essential supporting roles are played by ____________ ________.

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"neuron

glial cells"

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3 major classes of glia

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"astrocytes

oligodendrocytes

microglia"

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astrocytes

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"maintenance of the extracellular milieu (the composition, including the ion concentrations, of extracellular fluid in the brain) for healthy neuronal function

metabolism of certain neurotransmitters

formulation of the BBB
"

Front 34

which glia cell is critical for CNS response to injury

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astrocytes

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Oligodendrocytes

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produce myelin sheaths that encase axons and facilitate the conduction of AP

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microglia

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microglia, together with lymphocytes and macrophages that migrate to the CNS from the periphery, are the cellular components of the brains immune system

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_________ are a key component in guiding the migration of growing neurons during development

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glia

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3 main parts of a neron

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cell body, axon & dendrites

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grey matter vs white matter

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"grey matter: contains neural cell bodies

white matter: contains myelinated axon tracks (NO neural cell bodies)"

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organelle

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"a specialized subunit within a cell that has a specific funtion & is usually enclosed within its own lipid bilayer

the name organelle comes from the idea that these structures are to cells what an organ is to the body"

Front 41

eukaryotic organelles

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"cell type, in part organized smaller interior compartments that are themslves enclosed by lipid membranes that resemble the outermost cell membrane

not all eukaryotic cells have organelles

major eukaryotic organelles: endoplasmic reticulum, Golgi apparatus, mitochondria, vacuole, nucleus"

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Endoplasmic reticulum

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endoplasmic reticulum is a eukaryotic organelle that forms an interconnected network of tubules, vesicles, and cisternae within cells.

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rough endoplasmic reticulum

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Rough endoplasmic reticula synthesize proteins

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smooth endoplasmic reticulum

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smooth endoplasmic reticula synthesize lipids and steroids, metabolize carbohydrates and steroids (but not lipids), and regulate calcium concentration, drug metabolism, and attachment of receptors on cell membrane proteins

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Golgi apparatus

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"processes and packages macromolecules, such as proteins and lipids, after their synthesis and before they make their way to their destination;

it is particularly important in the processing of proteins for secretion."

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ribosome

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"is an an organelle the function of which is to assemble the twenty specific amino acid molecules to form the particular protein molecule determined by the nucleotide sequence of an RNA molecule

Ribosomes then read the information in this mRNA and use it to create proteins. This process is known as translation; the ribosome translates the genetic information from the RNA into proteins"

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cytoskeleton

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"is a cellular ""scaffolding"" or ""skeleton"" contained within the cytoplasm and is made out of protein.

The cytoskeleton is present in all cells"

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mitochondria

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"a membrane-enclosed organelle found in most eukaryotic cells

Mitochondria are sometimes described as ""cellular power plants"" because they generate most of the cell's supply of adenosine triphosphate (ATP), used as a source of chemical energy.

In addition to supplying cellular energy, mitochondria are involved in a range of other processes, such as signaling, cellular differentiation, cell death, as well as the control of the cell cycle and cell growth"

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macromolecules

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"A macromolecule is a very large molecule commonly created by some form of polymerization

the term is applied to the four conventional biopolymers (nucleic acids, proteins, carbohydrates, and lipids), as well as non-polymeric molecules with large molecular mass such as macrocycles"

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cytoplasm

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"a thick liquid residing b/w the cell membrane holding all the cell's internal sub-structures (called organelles) except for the nucleus.

The cytoplasm has 3 major elements: the cytosol, organelles, and inclusions"

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polymerization

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"polymerization is a process of reacting monomer molecules together in a chemical reaction to form three-dimensional networks or polymer chains.

There are many forms of polymerization and different systems exist to categorize them."

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polymer

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A polymer is a large molecule (macromolecule) composed of repeating structural units.

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monomer

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an atom or small molecule that may bind chemically to other monomers to form a polymer

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cell body's primary responsibility:

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synthesizing and producing proteins which are subsequently transported to their appropriate locations within the neuron

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nucleus contains:

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"genomic DNA that is transcribed into mRNA;

mRNA is exported from the nucleus to the cytoplasm where it is translated into protein on ribosomes"

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projection neurons

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neurons that send axons to another region of the CNS or to the periphery

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interneurons

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axons remain within the CNS region of origin

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axons also may give rise to recurrent collaterals that often serve _____________ ____________ __________

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feedback regulatory functions

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dendrites & cell body serve as the primary structure for

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the reception of synaptic contacts from other neurons

Front 60

Are dendritic spines fixed structures?

Back 60

"nope

neurons regulate the number and morphology of spines in response to neural activity and environmental signals"

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the main function of the dendritic tree is to:

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reception, processing, and integration of incoming synaptic communication

Front 62

can dendrites fire AP?

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yes, dendrites contain voltage-dependant ion channels and thus fire AP and actively propagate information to the soma.

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can dendrites alter neuronal function?

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yes, dendrites also contain a wide variety of intracellular signaling molecules that are activated during synaptic communication and alter neuronal function

Front 64

cytoskeleton

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represents the inner structure, or scaffold, of a neuron is formed by a system of interconnected molecular filaments termed microtubules, intermediate filaments, and actin filaments.

Front 65

microtubules

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"microtubules are made of polymers of tubulin (a globular protein that forms a heterdimer between alpha and beta tubulin)

microtubules copurify with several microtubule-associated proteins (MAPs), which have significant roles in the assembly of microtubules, in cross-linking them to other filaments, and in transport functions."

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"intermediate filaments of neurons
(neurofilaments)"

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formed by 3 polypeptide subunits of low, middle, and high molecular masses.

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actin filamens (aka microfilaments)

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made of actin (a globular protein) that self-assembles into a linear polymer

Front 68

microtubules and intermediate filaments are cross-linked to form a:

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microtubules and intermediate filaments are cross-linked to form a longitudinal scaffold for axons and dendrites

Front 69

actin microfilaments are heavily concentrated:

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"in dedritic spines and growth cones

(both of which are dynamic structures that can respond to extracellular signals by changing shapes)"

Front 70

the cytoskeleton not only has important structural functions, but also . . .

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controls the transport of proteins b/w the cell body and its axonal and dendritic processes

Front 71

what type of transport occurs in the axon?

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"fast anterograde: involves the movement of transport vesicles (used for functioning of the presynaptic terminal)

fast retrograde

slow anterograde"

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the power to move vesicles along microtubules by fast axonal transport is derived from two force-generating proteins:

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"kinesin: has intrisic polarity - moves vesicles only toward the plus end of microtubules and is therefore is the motor protein for anterograde fast transport

dynein: moves vesicles only toward the minus end and thus is the motor protein for retrograde fast transport

these proteins are ATPase that, by binding to microtubules, are stimulated to transport vesicles"

Front 73

do microtubulers have an intrinsic polarity?

Back 73

"yes

plus ends pointing toward the presynaptic terminals and minus ends pointing toward the cell body, they can serve as a compass to direct vesicle traffic"

Front 74

why retrograde axon transport functions?

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"to return various membrane molecules to the soma for elimination

and is important from nerve terminals to the soma"

Front 75

slow axon transport . .

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"not well understood

it appears to utilize the proteins that comprise the cytoskeleton itself - a dynamic rather than a static structure that is continually renewed"

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is the dendritic cytoskeleton different / same from that of the axons?

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"different

unlike axons, in which the polarity of microtubules is fixed, dendrites have microtubules whose polarity varies because equal number of microtubules are oriented in each direction

The proteins associated with dendritic microtubules also differs from those of axonal microtubules"

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where is MAP2 found?

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"only in dendrites and in the cell body

MAP2 is a protein involved in microtubule assembly - which is an essential step in neurogenesis

MAP2 serves to stabilize microtubules growth "

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where is protein tau found?

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"protein tau is found almost exclusively in axons

protein tau stabilizes microtubules"

Front 79

"the presynaptic and postsynaptic elements of a synapse are __________ ___________ to one another and to the extracellular matrix by means of numerous proteins (such as cell adhesion molecules [CAMs], cadherins, and integrins, and by astrocytes

"

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"tightly bound
"

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the presynaptic terminal contains

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"specialized cellular structures that allow it to remain metabolically and functionall independent from the neuronal cell body

it contains large numbers of mitochondria to provide energy, enzymes to synthesize and degrade NT, and synaptic vesicles to store substantial concentrations of NT while waiting for a signal to be released"

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phenytoin & carbamazepine (antiepileptic drugs) act by altering ____ channel kinetics

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Na+

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Lidocaine and procaine (common local anesthetics) block voltage gated _____ channels and prevent the conduction of nerve impulses that signal the occurrence of tissue damage and therefore pain.

Back 82

Na+

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inside a neuron, higher concentrations of ____

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K+, large proteins

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outside a neuron, higher concentrations of _____

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Na+, Ca++, and Cl-

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"evolutionarily, the maintenace of ionic gradients may have developed from a drive to maintain an extracellular enviroment similar to that of seawater.

Sea water possesses a similar K+ to Na+ to Cl- ratio"

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isn't that interesting. . .

Front 86

selective permeability of a cell membrane depends on . .

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the numbers and states of its various ion channels

Front 87

Nernst equation

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"determines the equilibrium potential

Em = 58 x log (K0 / K1)
where Em is the equilibrium membrane potential
K0 is the concentration of K+ ions outside the cell
K1 is the concentration of K+ ions inside the cell
"

Front 88

cell membrane is far more permeable to _____ than to any other ion

Back 88

K+

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the true equalibrium potential lies between

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"likes somewhere between the equilbrium potential for the various ions

but because K+ is the most permeable vs the othe ions, the neurons resting potential is much closer to the equalibrium potential than it is to Na+ or Cl-"

Front 90

when one ion channel opens, it drives the membrane potential . . .

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toward the equilibrium potential of that ion

Front 91

goldman equation

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"determines the equilibrium potential but takes into account all of the ions that are permeant to that membrane

it is Nerst like"