Transcript Unit 3-1 Nervous System Pt 1 Notes File

Cell Signaling
A signal transduction pathway - is a series of steps by which a signal on a cell’s surface is
converted into a specific cellular response
Signal transduction pathways convert signals on a cell’s surface into cellular responses
Local and Long-Distance Signaling
Cells communicate by chemical messengers
• Cell (gap) junctions that directly connect the
cytoplasm of adjacent cells
• direct contact, or cell-cell recognition
Paracrine system
• messenger molecules that travel only short distances
Endocrine system: Hormones = long-distance signaling.
• Chemical messengers secreted into vascular system
 transported to long-distance target
Stages of Cell Signaling
1.
2.
3.
4.
Reception
Transduction
Response
Termination
I. Reception: A signal molecule binds to a receptor protein, causing it to change shape
• The binding between a signal molecule (ligand) and receptor is highly specific
• A shape change in a receptor is often the initial transduction of the signal
• Most signal receptors are plasma membrane proteins
Receptors in the Plasma Membrane
• Most water-soluble signal molecules bind to specific sites on receptor proteins in the
plasma membrane
• There are three main types of membrane receptors:
1. G protein-coupled receptor
• a plasma membrane receptor that works with the help of a G protein
• The G protein acts as an on/off switch: If GDP is bound to the G protein, the G protein is inactive
2. Receptor Tyrosine Kinases
• membrane receptors that
attach phosphates to tyrosines
• A receptor tyrosine kinase can
trigger multiple signal
transduction pathways at once
3. Ligand-gated Ion Channels
• A receptor acts as a gate
• When a signal molecule binds as a ligand to the receptor,
the gate allows specific ions, such as Na+ or Ca2+,
through a channel in the receptor
Intracellular Receptors
• Some receptor proteins are intracellular, found in the
cytosol or nucleus of target cells
• Small or hydrophobic chemical messengers cross
membrane and activate receptors
• Ex: steroids & thyroid hormones
• An activated hormone-receptor complex can act as a
transcription factor, turning on specific genes
II. Transduction: Cascades of molecular interactions relay signals from receptors to target
molecules in the cell
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Signal transduction usually multi-step process
Signal amplification: can often amplify a signal
provide more opportunities for coordination and regulation of the cellular response
relays are mostly proteins
Signal Cascade: Like falling dominoes, once started all subsequent steps will occur
At each step, the signal is transduced into a different form, usually a shape change in a protein
Protein Phosphorylation
and Dephosphorylation
• In many pathways, the signal is
transmitted by a cascade of protein
phosphorylations
• Protein kinases transfer phosphates
from ATP to protein
Small Molecules and Ions as Second Messengers
• The extracellular signal molecule that binds to the receptor is a pathway’s “first messenger”
• Second messengers are small, nonprotein, water-soluble molecules or ions that spread
throughout a cell by diffusion
• Second messengers participate in pathways initiated by G protein-coupled receptors and
receptor tyrosine kinases
• Cyclic AMP and calcium ions are common second messengers
- Cyclic AMP (cAMP) is one of the most widely used second messengers
- Adenylyl cyclase, an enzyme in the plasma membrane, converts ATP to cAMP in response
to an extracellular signal
• Calcium is an important second
messenger because cells can regulate
its concentration
• A signal relayed by a signal
transduction pathway may trigger an
increase in calcium in the cytosol
• Pathways leading to the release of
calcium involve inositol triphosphate
(IP3) and diacylglycerol (DAG) as
additional second messengers
Signal Amplification
• Enzyme cascades amplify the cell’s response
• At each step, the number of activated products is much greater than in the preceding step
III. Cell specificity & Response
• Different kinds of cells have different
collections of proteins
• These different proteins allow cells to detect
and respond to different signals
• Even the same signal can have different effects
in cells with different proteins and pathways
• Pathway branching and “cross-talk” further
help the cell coordinate incoming signals
• Ultimately, leads to regulation of cellular
activities
• may occur in cytoplasm or nucleus
• Many regulate synthesis of enzymes or other
proteins, usually by turning genes on or off in
the nucleus
ex: final activated molecule may function as a
transcription factor
ex: activation of enzyme
ex: alters cell characteristics
IV. Termination of the Signal
• Inactivation mechanisms are an essential aspect of cell signaling
• When signal molecules leave the receptor, the receptor reverts to its inactive state
Types of Nervous Systems
Nerve Net: series of interconnected nerve cells
• Simplest form
• No clustering of neurons
• Neurons are interconnected
• Excitation of 1 neuron results in coordinated excitiation
Cephalization: Neurons clustered to anterior into sensory organs
• Segmental = repeating patterns
• central nervous system (CNS) consists of a brain and longitudinal nerve cords
• The peripheral nervous system (PNS) is composed of nerves and ganglia
Histology of Nervous Tissue (microscopic anatomy)
Neurons - nerve cells
1. Cell body- like most cells --Focal point for outgrowth of neuron processes(extensions)
• Nuclei - clusters of cell bodies in CNS
• Ganglia - clusters of cell bodies in PNS
2. Dendrites -neuron processes(extensions) – Input Regions
• Short, tapering, and branched
• Electrical signals are conveyed as graded potentials (not action potentials)
3. Axon - neuron processes – Conducting region (convey signal)
• Slender processes of uniform diameter arising from the hillock
• Long axons are called nerve fibers
• Usually 1 unbranched per neuron
• Rare branches, if present, are called axon collaterals
• Axon terminal = terminal boutoun – Transmits signal
branched terminus of an axon
Secretory Region - neurotransmitters (chemicals)
• Tracts - bundles of axons in CNS
• Nerves - bundles of axons in PNS
Neuroglia = glial cells - supporting cells ,protection
Segregate and insulate neurons
In CNS - Astrocytes , Microglia, Ependymal , Oligodendrocytes
In PNS - Satellite cells , Schwann -> myelin sheaths
myelin sheath
hillock
Node of Ranvier
(Cell Body)
Multipolar
Bipolar
Unipolar
Neurons have a membrane potential (Volts)
•Electrical Potential (Difference in electrical charge)
•Membrane is Polar
•Cell potential usually -40 to -90 mV (minus because inside is more negatively charged)
•Generated by differences in ion conc. (Na+ K+ , Cl-, protein anions A-)
•Ion concentrations are changed by Na+ K+ pump
Na+/K+
ATPase
Membrane protein Functions: The Na/K-pump
• Always on
• Makes electrochemical gradient
Outside +
Inside -
High Na+ outside
High K+ inside
etc
Membrane Potential: Difference in charge or voltage
Subtle detail: absolute charge cannot be measured, only difference can. So actually
measuring both inside and out and the positive charge outside matters
Cell is polarized
Inside negative outside positive
Resting Membrane Potential
Inactive other than pumps
(Time)
• Pumps generate Resting membrane potential
= charge of the cell
resting = no channels open
• Every time all other channels are closed and
membrane returns to normal it is due to the pump
• Signaling in neurons by Changes in Membrane Potential
• Brief changes in membrane potential are due to changes in membrane permeability
• Regulated ion channels – are Sometime open sometimes closed
Graded Potentials:
receptor potentials, generator potentials, postsynaptic potentials
• Magnitude varies directly (graded) with stimulus strength
• Decrease in magnitude with distance as ions flow and diffuse through leakage channels
• Short-distance signals
Changes in Potentials
•The electrical signal of a neuron is spread using the depolarization of the membrane potential along
the axon
•Generated by Gated-Membrane Ion Channels (changes membrane permeability)
Example: ach - Na+-K+ gated channel
•Closed when no neurotransmitter
Na+ cannot enter the cell
K+ cannot exit the cell
•Open when a neurotransmitter is attached to the
receptor
Na+ enters the cell
K+ exits the cell
Example: Na+ channel
•Closed when the intracellular environment
is negative
Na+ cannot enter the cell
•Open with electrical stimulus (potential
changes)
Na+ can enter the cell
What happens when sodium channels open?
Depolarization of membrane potential (inside becomes less neg)
+++
+++
---
--Original concentrations
restablished
Hyperpolarization – opposite of depolarization when
membrane becomes even more negative than usual
Graded Potentials
•Short-lived (become repolarized quickly), local changes in membrane potential
•Decrease in intensity with distance (the further out the less change in charge)
•Magnitude varies directly with the strength of the stimulus
•Sufficiently strong graded potentials can initiate action potentials
1.
2.
Must have the right voltage gated channels
Must pass threshold (about 10-15mV above resting potential)
Threshold
+++
+++
---
---
-55
Excitatory Postsynaptic Potentials
•EPSPs are graded potentials that can initiate an action potential in an axon
•Use only chemically gated channels
•Na+ and K+ flow in opposite directions at the same time
•Postsynaptic membranes do not generate action potentials
Graded
Potential
Inhibitory Synapses and IPSPs (inhibitory postsynaptic potentials)
•Neurotransmitter binding to a receptor at inhibitory synapses:
1. Causes the membrane to become more permeable to potassium and chloride ions
2. Leaves the charge on the inner surface negative
3. Reduces the postsynaptic neuron’s ability to produce an action potential
Also Graded
Potential, but
negative