Vertebrate Physiology Exam 2

receptors

chemical messengers bind to specific target-cell

water-soluble messengers

bind at the plasma membrane

lipid-soluble messengers

bind intracellularly (cytosol or nucleus)

signal transduction

binding alters receptor conformation, triggering a cellular response

receptor

a specific protein in either the plasma membrane or the interior of a target cell that a chemical messenger binds with, thereby invoking a biologically relevant response in that cell

specificity

-the ability of a receptor to bind only one type or a limited number of structurally related types of chemical messengers

-only cells that express the correct receptor can bind a particular messenger

saturation

the degree to which receptors are occupied by messengers

affinity

the strength with which a chemical messenger binds to its receptor

competition

the ability of different molecules to compete with a ligand for binding to its receptor

antagonist

a molecule that competes with a ligand for binding to its receptor but does not activate signaling normally associated with the natural ligand

agonist

-a chemical messenger that binds to a receptor and triggers the cell’s response

-often refers to a drug that mimics a normal messenger’s action

down-regulation

-a decrease in the total number of target-cell receptors for a given messenger

-may occur in response to chronic high extracellular concentration of the messenger

up-regulation

-an increase in the total number of target-cell receptors for a given messenger

-may occur in response to a chronic low extracellular concentration of the messenger

increased sensitivity

-the increased responsiveness of a target cell to a given messenger

-may result from up-regulation of receptors

down-regulation

-a decrease in the number of receptors on a target cell, due to the presence of long-term high messenger concentration

-decreases the cell’s responsiveness, by desensitizing the cell to the messenger

-aided by internalization

internalization

entry of the messenger receptor complex by endocytosis, and subsequent degradation or storage for future use

up-regulation

-an increase in the number of receptors on a target cell, due to the presence of long-term low messenger concentration

-increases the cell’s responsiveness, by causing supersensitivity of the cell to the messenger

-aided by insertion of stored vesicle-bound receptors into the cell membrane when needed

lipid-soluble messengers

-they can diffuse through the plasma membrane

-they have intracellular receptors

-the signal-receptor complexes bind directly to recognized sequences in the DNA and alter gene transcription

water-soluble messengers

-a broad range of receptors: ion channels, G-protein coupled receptors, receptors with intrinsic kinase activity

-various receptors activate intracellular signaling cascades that affect cell function

-activate downstream mediators, which affect DNA transcription, and have other effects in the cell

-require second messengers to carry out their effects, since they cannot penetrate the plasma membrane

receptors that are ligand-gated ion channels

-first messenger binds in the plasma membrane, causing it to open

-specific ions diffuse through the open channel

-this ion movement changes the cell’s membrane potential

receptors that function as enzymes

-a messenger binds to a receptor tyrosine kinase, altering its confirmation and activating its cytoplasmic enzymatic domain

-the activated receptor autophosphorylates its own tyrosine residues

-the resulting phosphotyrosines serve as docking sites for cytoplasmic proteins

-docked proteins activate subsequent proteins via sequential phosphorylation, triggering cellular signaling pathways

cyclic GMP (cGMP)

the receptor functions as both a receptor and as a guanylyl cyclase, which catalyzes the formation, in the cytoplasm, of a molecule of

cGMP-dependent protein kinase

cGMP functions as a second messenger to activate an enzyme called

receptors that interact with cytoplasmic janus kinases

-receptors lacking intrinsic kinase activity associate with separate cytoplasmic janus kinases (JAKs)

-first messenger binding alters the receptor’s conformation, activating the associated JAK

-activated JAKs phosphorylate target proteins, driving the synthesis of new proteins that mediate the cellular response

-this mechanism primarily facilitates signaling for immune system cytokines

G protein-coupled receptors

-protein complexes bound to inactivate receptors on the cytosolic surface of the plasma membrane

-contain 3 subunits, called alpha, beta, and gamma subunits

-the binding of a first messenger to the receptor changes receptor conformation, and the activated receptor increases the affinity of the alpha subunit for GTP

-when bound to GTP, the alpha subunit dissociated from the other subunits of the trimeric

-this dissociation allows the activated alpha subunit to link up with another plasma membrane protein, either an ion channel or an enzyme

-these ion channels and enzymes mediate the next steps that lead to the cell’s response

-these are the most numerous type of receptors and have a large variety of signaling pathways associated with them

alpha subunit

can bind GDP and GTP

beta and gamma subunits

anchor the alpha subunit in the membrane

adenylyl cyclase and cyclic AMP

-activation of the receptor by the binding of the first messenger allows the receptor to activate its associated G protein

-this causes Gs to activate its effector protein, the plasma membrane enzyme adenylyl cyclase

-the activated adenylyl cyclase catalyzes the conversion of cytosolic ATP molecules to cyclic 3’ ,5’-adenosine monophosphate, or cyclic AMP (cAMP)

-cyclic AMP then acts as a second messenger

cAMP phosphodiesterase

cAMP action terminates when it is broken down to AMP by the enzyme

rate of synthesis or breakdown

the cellular concentration of cAMP can be changed either by altering its

Gi protein-coupled receptors

-not all G proteins stimulate cAMP formation; some inhibit adenylyl cyclase

-this occurs because these receptors are associated with a different G protein

-activation causes the inhibition of adenylyl cyclase

-this result is to decrease the concentration of cAMP in the cell and thereby the phosphorylation of key proteins inside the cell

control of ion channels by G proteins

-an ion channel can be the effector protein for a G protein and can be directly or indirectly regulated

-the ion channels can be either opened or closed by this mechanism

-in direct regulation, the G protein interacts with the channel without any second messengers being involved

-in indirect regulation, second-messenger pathways are used

Gq

a G protein called ____ is activated by a receptor bound to a first messenger

phospholipase C (PLC)

activated Gq then activates a plasma membrane effector enzyme called

diacylglycerol (DAG) and inositol triphosphate (IP3)

PLC catalyzes the breakdown of the plasma membrane phospholipid phosphatidylinositol bisphosphate (PIP2)

second messengers

both DAG and IP3 then function as _____ but in very different ways

protein kinase C

DAG activates a family of protein kinases collectively called ___, which then phosphorylate a large number of other proteins, leading to the cell’s response

endoplasmic reticulum

cytosolic IP3 binds to receptors located on the

IP3

these receptors are ligand-gated Ca2+ channels that open when bound to ___ resulting in increased cytosolic Ca2+ concentration

protein kinase C

one of the actions of Ca2+ is to help activate some forms of

Ca2+ as a second messenger

-functions as a second messenger and directly interacts with other signaling proteins

-active transport systems in the plasma membrane and organelles maintain extremely low cytosolic concentrations

-a large electrochemical gradient favors diffusion into the cytosol through channels in the plasma membrane and endoplasmic reticulum

-increases or decreases in cytosolic levels elicit specific cellular responses, including changes in membrane potential

calcium-calmodulin

on binding with Ca2+, calmodulin changes shape, allowing ____ to activate or inhibit a large variety of enzymes and other proteins, many of them protein kinases

calmodulin-dependent protein kinases

activation or inhibition of these ____ leads, via phosphorylation, to activation or inhibition of proteins involved in the cell’s responses to the first messenger

eicosanoids

a family of molecules produced from the polyunsaturated fatty acid arachidonic acid, which is present in plasma membrane phospholipids

cyclic endoperoxides, prostaglandins, thromboxanes, and leukotrienes

the eicosanoids include the ______ and are generated in many kinds of cells in response to different types of extracellular signals

phospholipase A2 (PLA2)

the synthesis of eicosanoids begins when a stimulus binds to its receptors and activates ___, an enzyme in the plasma membrane of the stimulated cell

PLA2

splits off arachidonic acid from the membrane phospholipids, and arachidonic acid can then be metabolized by two pathways (cyclooxygenase and lipoxygenase)

cyclooxygenase (COX)

one pathway arachidonic acid is metabolized is initiated by the enzyme ___ and leads to formation of the cyclic endoperoxides, prostaglandins, and thromboxanes

lipoxygenase

the other pathway arachidonic acid is metabolized is initiated by the enzyme ____ and leads to formation of the leukotrienes

eicosanoids

-may act as intracellular messengers, but more often they are released immediately and act locally

-after acting, they are quickly metabolized and inactivated by local enzymes

-they exert a wide array of effects, particularly on blood vessels and in inflammation

first messenger removal, second messenger reduction, and receptor inactivation

signal termination prevents chronic cellular overstimulation through three primary mechanisms

first messenger removal

enzymatic degradation, cellular uptake, or diffusion

second messenger reduction

enzymatic breakdown (ex via cAMP phosphodiesterase)

receptor inactivation

phosphorylation to decrease messenger affinity or block G-protein binding

-internalization via endocytosis

central nervous system

the brain and spinal cord

peripheral nervous system

the nerves that connect the brain or spinal cord with other organs and tissues

neuron

the functional unit of the nervous system, which generates electrical signals called action potentials or nerve impulses

glial cells

non neuronal cells that support neurons

parts of a neuron

cell body (soma), dendrites, axon, initial segment (axon hillock), and axon terminal (synaptic knob)

cell body (soma)

contains nucleus and ribosomes

dendrites

branches that recieve information, typically through neurotransmitters

axon

carries outgoing signals to target cells

initial segment (axon hillock)

portion of axon that arises from cell body; generates action potentials

axon terminal (synaptic knob)

end of each branch; releases neurotransmitters

schwann cells

in the PNS, glial cells called ___ form individual myelin sheaths surrounding 1- to 1.5- millimeters long segments at regular intervals along some axons

myelin sheath

-speeds up conduction of the electrical signals along the axon and conserves energy

-act as electrical insulators, preventing ions from crossing the cell membrane and electrical current from flowing

nodes of ranvier

the gaps between regions of the myelin sheath are the ___ and they are areas that permit the exchange of Na+ and K+ ions across the cell membrane

anterograde (forward)

kinesins move nutrients, vesicles, and mitochondria from the soma to axon terminals (cell body to terminals)

retrograde (backward)

dyneins move recycles factors and vesicles toward the soma and this is also a pathway for pathogens (terminal to cell body)

afferent neurons (sensory)

-transmit information into the NS from receptors at their peripheral endings

-single process from the cell body splits into a long peripheral process (axon) that is in the PNS and a short central process (axon) the enters the CNS

efferent neurons (motor)

-transmit information out of the CNS to effector cells, particularly muscles, glands, neurons, and other cells

-cell body with multiple dendrites and a small segment of the axon are in the CNS; most of the axon is in the PNS

interneurons

-function as integrators and signal changers

-integrate groups of afferent and efferent neurons into reflux circuits

-lie entirely within the CNS

-account for >99% of all neurons

glial cells

provide neurons with physical and metabolic support

types of glial cells in the CNS

astrocytes, microglia, ependymal cells, and oligodendrocytes

astrocytes

help regulate the composition of the extracellular fluid in the CNS by removing potassium ions and neurotransmitters around synapses, stimulate the formation of tight junctions, and sustain neurons metabolically

microglia

specialized, macrophage-like cells that perform immune functions in the CNS and may also contribute to synapse remodeling and plasticity

ependymal cells

line the fluid-filled cavities within the brain and spinal cord and regulate the production and flow of cerebrospinal fluid

oligodendrocytes

form the myelin sheath of CNS axons

neurogenesis and migration

stem cells differentiate into neurons or glia, migrate to target locations, and extend axons and dendrites

axonal growth and synaptogenesis

axon growth cones navigate along glial cells, guided by cell adhesion molecules and neurotrophic factors, to reach targets and form synapses

vulnerability

fetal and infant neural development is highly susceptible to permanent damage from toxins, radiation, malnutrition, and pathogens

plasticity and stability

while basic mature central nervous system circuits remain fixed, lifelong neuroplasticity persists through continuous synaptic creation and pruning, though this capacity decreases with age

peripheral nervous system repair

-axons can regenerate if the cell body remains intact

-the disconnected distal segment degenerates, while the proximal end forms a growth cone that regrows at approximately 1mm/day to eventually restore function

central nervous system crush injuries

-spinal injuries typically crush rather than sever tissue

-this causes oligodendrocytes apoptosis and demyelination, blocking effective signal transmission despite intact axons

CNS severed axons

severed CNS axons cannot significantly regenerate across a damaged site, resulting in permanent loss of function

resting membrane potential

-the potential difference across the plasma membrane of a neuron when it is at rest

-inside of neurons is negatively charged with respect to outside

-the magnitude in neurons is typically -40 to -90 millivolts, with the negative sign designating that the inside of the neuron is negative compared to the outside

-changes in potential are due to movement of ions

-exists due to an excess of negative ions inside the neuron and an excess of positive ions outside the cell

development of a resting membrane potential

-the Na+/K+ ATPase pump establishes the concentration gradients and generates a small negative potential, that keep the resting potential at -70mV

-greater net movement of K+ than Na+ across the membrane makes the resting membrane potential more negative on the inside of the cell

-any small influx of Na+ ions is balances by an efflux of K+ ions through K+ leak channels, then the Na+/K+ ATPase pump transports both types of ions back to their origiinal locations and concentrations

-when an action potential occurs, the pump returns Na+/K+ ions to their original locations after depolarization and repolarization

depolarization

refers to the potential moving from RMP to less negative values

overshoot

refers to a reversal of membrane polarity, when the inside of the cell becomes more positive than the outside

repolarization

refers to the potential returning to the RMP from a depolarized state

hyperpolarization

refers to the potential becoming more negative than the RMP

equilibrium potential

the voltage difference across a membrane that produces a flux of a given ion species that is equal but opposite to the flux due to the concentration gradient of that same ion

synaptic potential

a graded potential change produced in the postsynaptic neuron in response to the release of a neurotransmitter by a presynaptic terminal; may be depolarizing or hyperpolarizing

receptor potential

a graded potential produced at the peripheral endings of afferent neurons in response to a stimulus

pacemaker potential

a spontaneously occurring graded potential change that occurs in certain specialized cells

threshold potential

the membrane potential at which an action potential is initiated

graded potentials

-changes in membrane potential that are confined to a small region of the plasma membrane

-the magnitude of the potential change can vary

decremental

potential change decreases as the distance from the site of the original event increases

summation

-addition of graded potentials from several stimuli, that occur in rapid succession, before each graded potential had died out

-this of several small potentials can aid in integration, and in reaching the threshold potential, so an action potential will occur

action potential

-large alterations in the membrane potential; the membrane potential may change by as much as 100 millivolts

-generally very rapid and may repeat at frequencies of several hundred per second