1/62
Looks like no tags are added yet.
Name | Mastery | Learn | Test | Matching | Spaced |
|---|
No study sessions yet.
What are the types of signals in Cell-Cell communication?
Electrical signals
chemical signals
Electrical signals
changes in a cell's membrane potential
- action potentials
- - within a cell
--- from cell to cell
Chemical signals
secretion of chemicals into ECF
- hormones: insulin
- paracrin and autocrine agents
-- nitric oxide in arterioles
-- histamine in stomach and immune system
responsible for most communication within the body.
chemical signals act as ligands that bind to proteins to initiate a response.
Target cells
cells that respond to electrical or chemical signals
What are the 4 basic methods of cell to cell communication?
Local communication
1. gap junctions: allow direct cytoplasmic transfer of electrical and chemical signals between adjacent cells
2. contact-dependent signals: occur when surface molecules on one cell membrane bind to surface molecules on another cell's membrane
3. chemicals that diffuse through the ECF to act on cells close by
4. Long distance communication: uses a combination of chemical and electrical signals carried by nerve cells and chemical signals transported in the blood.
Gap junctions
simplest
protein channels that create cytoplasmic bridges between adjacent cells
forms from the union of membrane-spanning proteins, called connexins. The united connexins create a protein channel (connexon) that can open and close.
when the channel is open, the connected cells function like a single cell that contains multiple nuclei
When gap junctions are open, what happens?
ions and small molecules like a.a.'s, ATP, cAMP diffused directly from the cytoplasm of one cell to the cytoplasm of the next.
larger molecules can't pass through gap junctions.
gap junctions are the only means by which electrical signals can pass DIRECTLY from cell to cell.
Contact dependent signals
- require cell-cell contact
surface molecules on one cell membrane bind to a membrane protein of another cell
this occurs in the immune system and during growth/development
CAMs act as receptors in cell-cell signaling
- they are linked to the cytoskeleton or to intracellular enzymes and through these linkages, CAMs transfer signals in both directions across cell membranes
Paracrine signal
is a chemical that acts on cells in the immediate vicinity of the cell that secreted the signal
i.e. histamine
Autocrine signal
a chemical signal that acts on the cell that secreted it
How do paracrine and autocrine signal molecules reach their target?
by diffusing through interstitial fluid
Endocrine System
communicates by using hormones, chemical signals that are secreted into the blood and distributed all over the body by circulation
hormones come into contact with most cells of the body, but only those cells with receptors for the hormone are target cells.
Nervous system
uses combo of chemical and electrical signals to communicate over long distances.
electrical signal travels along neuron until reaches end of cell, where its translated into a chemical signal (NT) secreted by the neuron (aka neurocrine molecule)
Neurotransmitter
a neurocrine molecule that diffuses from the neuron across a narrow extracellular space to a target cell and has rapid onset effect.
ACh
Neuromodulator
when a neurocrine acts more slowly as an autocrine or paracrine
- somatostatin
Neurohormone
a neurocrine molecules that diffuses into the blood for body-wide distribution
- hypothalamus & post. pit hormones
Cytokines
class of regulatory proteins
act as both local and long distance
produced by all nucleated cells when stimulated (made on demand)
local signals: cell development and differentiation
long distance signals: immune system and inflammatory response
Grey areas
neurohormones and hormones - blurs endocrine and nervous systems
cytokines and hormones: overlap in function blurs distinction
Why do some cells respond to a chemical signal while other cells ignore it? Receptor proteins
A cell can respond to a particular chemical signal only if the cell has the appropriate receptor protein to bind that signal.
Requirements of a signal pathway
1. the signal molecule is a ligand that binds to a protein receptor. The ligand is also known as a first messenger because it brings info to the target cell
2. ligand-receptor binding activates the receptor
3. The receptor in turn activates one or more intracellular signal molecules
4. the last signal molecules in the pathway creates a response by modifying existing proteins or initiating the synthesis of new proteins.
Simple 5 steps of signal pathways
signal molecule binds to membrane protein receptor which activates intracellular signal molecules with alter target proteins to create a response
Intracellular receptor proteins
cytosol or nucleus
they regulate protein synthesis
have to have a lipophilic ligand because the membrane is lipid (simple diffusion into cell)
once inside, they bind to cytosolic or nuclear receptors
What does activation of intracellular receptor proteins do?
often turns on a gene and directs the nucleus to make new mRNA
sometimes it can also repress or turn off gene activity
Lipophobic signal molecules
unable to enter cells by simple diffusion.
they remain in the ECF and bind to receptor proteins on the cell membrane
usually response time is very rapid
What is signal transduction?
the process by which an extracellular signal molecule activates a membrane receptor that in turn alters intracellular molecules to create a response.
the extracellular signal molecule is the 1st messenger and the intracellular molecules are the 2nd messenger.
Biological signal transduction
1. first messenger (extracellular signal molecule) binds to and activates membrane receptor or
2. transducer
The activated membrane receptor turns on its associated proteins and starts an intracellular cascade of
3. second messenger system
the last second messenger in the cascade acts on intracellular
4. targets
to create a
5. response
Detailed basic transduction pathway
1. membrane receptors and their associated proteins usually either:
- activate protein kinases, which are enzymes that transfer a phosphate group from ATP to protein. or
- activate amplifier enzymes that create intracellular second messengers.
2. second messengers in turn
- alter the gating of ion channels, opening or closing ion channels creates electrical signals by altering the cells' membrane potential
- increase intracellular calcium, which binds to proteins and changes their function creating cellular response
- change enzyme activity, especially of protein kinases or protein phosphatasases (dephosph) which changes conformation and triggers response
3. the proteins modified by calcium binding and phosph. are responsible for the cells' response to the signal. (i.e. increased or decreased enzyme activity and opening/closing of gated ion channels)
Cascade
starts when a stimulus converts inactive molecule A (receptor) to active form. Active A converts B to activve and so on until final step substrate converted to product.
results in signal transformation/transduction
or signal amplification
What is are two amplifier enzymes?
tyrosine kinase
phosphorylates target protein
and
guanylyl cyclase
converts GTP to cGMP and phosphorylates target protein
Receptor enzymes may be intrinsic...meaning?
kinases may be intrinsic: part of the receptor protein
JAK kinase: a separate cytosol kinase activated by the receptor.
The activation of ___________ initiates the most rapid intracellular responses of all receptors.
receptor channels
Signal transduction using ion channels
1. receptor channels open or close in response to signal molecule binding
2. some channels are directly linked to G proteins
3. other channels respond to intracellular 2nd messengers
4. electrical or mechanical signals also open or close ion channels
G protein coupled receptors (GPCRs)
large and complex family of membrane spanning proteins that cross the p-lipid bilayer 7 times
the cytoplasmic tail of the receptor protein is linked to a 3 part membrane transducer molecule called the G protein.
When G proteins are activated by exchanging GDP for GTP, what do they do?
1. open an ion channel in the membrane or 2. alter enzyme activity on the cytoplasmic side of the membrane (alter an amplifier protein)
- most common signal transduction pway
GPCR-cAMP pathways
- adenylyl cyclase
adenylyl cyclase: amplifier enzyme: ATP--> cAMP
1. signal molecule binds to GPCR which activates G protein
2. G protein turns on adenylyl cyclase (amplifier enzyme)
3. adenylyl cyclase converts ATP to cAMP
4. cAMP activates protein kinase A
5. protein kinase A phosphorylates other proteins, leading ultimately to cellular response
GPCR - lipids Phospholipase C Transduction
1. signal molecule activates receptor and associated G protein
2. G protein activates phospholipase C (PLC) an amplifier enzyme
3. PLC converts membrane phospholipids into DAG, which remains in the membrane and IP3 which diffuses into the cytoplasm
4. DAG activates protein kinase C (PKC) which phosphorylates proteins
5. IP3 causes release of Ca2+ from organells, creating a Ca2+ signal
What are the two regions of a receptor enzyme?
a receptor region in the extracellular side of the cell memb. and enzyme region on cytoplasmic side.
Integrins
membrane spanning proteins that mediate blood clotting, wound repair, cell adhesion and recognition in the immune response, and cell movement during development.
on the extracellular side of membrane, integrin receptors bind either to proteins of extracellular matrix or to ligands like antibodies and molecules involved in blood clotting.
inside the cell, they attach to cytoskeleton via anchor proteins.
ligand binding to the receptor causes integrins to activate intracellular enzymes or alter the organization of the cytoskeleton.
big pic:
alter structure of cytoskeleton
activate intracellular enzymes
What is the importance of receptor channels and ion flow?
rapid response: most direct effect
alters cell membrane potential via ion movement
ACh receptor: ligand or chemical gated channel
- cation channel allows Na (enters cell) and K (leaves cell) to move
-- Na gradient is stronger, so net entry of Na+ (+) depolarizes the cell (eventually results in muscle contraction)
Others use 2nd messenger system: GPCRs
- activated G protein directly opens gated ion channels
- 2nd messenger opens gated ion channels
Calcium as a signal molecule
It is higher conc in ECF
enters the cell through Ca2+ channels that might be voltage gated, ligand gated, mechanically gated
can also be released from intracellular compartments by second messengers like IP3. Most intracellular Ca2+ is stored in the ER.
Several events occur
Gases as signal molecules: Nitric oxide (NO)
causes vasodilation
it is a neurotransmitter and neuromodulator (CNS)
Gases as signal molecules: carbon monoxide (CO)
Vasodilation
Neurotransmitter (CNS)
Gases as signal molecules: hydrogen sulfide (H2S)
Vasodilation
Lipids as signal molecules: Eicosanoid paracrine agents
derived from arachidonic acid
leukotreines: produced by WBCs
- stimulate asthma response, anaphylaxis
prostanoids: prostaglandins and thromboxanes
- act on: smooth muscle, pain, inflammation, bone, platelets
Multiple receptors have receptor isoforms, what do they do?
different receptor isoforms elicit different responses w/same ligand
Examples of receptor isoforms?
alpha adrenergic receptor w/ epinephrine: vasoconstriction
beta adrenergic receptor w/epinephrine: vasodilation
Parasympathetic (rest&digest) what type of adrenergic receptor do we want here?
want blood flow to be sent to digest part, so we want alpha adrenergic receptors
Sympathetic (fight or flight) what type of adrenergic receptor do we want here?
blood flow focused on muscles, decrease flow to digestion/reproduction
want beta (vasodilate)
Epinephrine and norepinepherine compete with each other because they both bind to adrenergic receptors. Which adrenergic receptor has a higher affinity for which compound?
Alpha higher affinity for norepinephrine
beta higher affinity for epinephrine
Agonist v antagonist
agonist: competing ligand binds and elicits response
antagonist: binds and blocks receptor activity
Up and Down regulation allows cells to modulate responses...what are they?
Down regulation: a decrease in receptor number. (can physically remove receptors by endocytosis or by desensitization
UP regulation: target cell inserts more receptors in the membrane, like if a neuron is damaged and unable to release normal amounts of NT.
How can a signal pathway be terminated?
1. By enzymatic hydrolysis of the ligand (it is broken down)
2. by diffusion of the ligand
3. by re-uptake of the ligand (seen in neurons, some NTs are reuptaken)
4. endocytosis of receptor-ligand complex
5. blocking a signal pathway
6. channel blocker drugs
Channel blocker drugs: receptor antagonists
1. B2-adrenergic receptor blockers (beta blockers)
2. H2-histamine receptor agonists
B2-adrenergic receptor blockers (beta blockers)
BP/heart issues and calcium channel blockers - congestive heart failure, hypertension
beta increases heart rate and makes it beat harder, so in people with heart issues you don't want that, so you use beta blockers to stop this.
H2-histamine receptor agonists
GERD and ulcers
histamine promotes release of acid , so that is why people take drugs to block that if they have GERD or ulcers.
What are Cannon's Postulates?
describe regulated variables and control systems
1. The NS has a role in preserving the fitness of the internal environment; NS integrates and coordinates the internal environment (endocrine does too though)
2. Body systems with tonic (constant level that can be modified up or down) control have a baseline of activity
- can increase or decrease activity as necessary
i.e. blood vessels: regulated by sympathetic, routinely somewhat vasoconstricted, sympathetic tells it to constrict more or less.
3. Some body systems have antagonistic control mechanisms
- autonomic control varies between the parasympathetic and sympathetic systems
4. some chemical signals can have different effects in different locations
- alternate receptors - receptor isoforms
Which two systems do long-distance reflex pathways include?
NS and endocrine
also cytokines can participate
What are the 3 major components of reflex pathway response loops?
input, integration, output
subdivided into:
1. stimulus
2. sensor/receptor
3. input signal
4. integrating center
5. output signal
6. target
7. response
Simple endocrine reflex pathway
1. internal or external change
2. endocrine system sensor- integrating center
3. output signal: hormone
4. target
5. response
Simple neural reflex
1. internal or external change
2. receptor
3. input signal: sensory neuron
4. Nervous system integrating center
5. efferent neuron
6. target
7. response
Complex neuro-endocrine reflex
1. internal or external change
2. receptor
3. input signal: sensory neuron
4. nervous system integrating center
5. efferent neuron or neurohormone
6. endocrine integrating center
7. output signal #2: hormone
8. target
9. response
Which type of reflex is most general? most specific?
endocrine
neural
Neurohormone reflex
same as neural except that the neurohormone released by neuron travels in the blood to the target like a hormone
like release of breast milk in response to baby suckling