General Physiology Exam 1

Phosphodiesterase

The enzyme that breaks cAMP down into AMP

This enzyme is always active, so cAMP will only ever rise when Adenylyl Cyclase is activated

Transducing Domain

The domain of the receptor that regulates receptor response

Protein Kinase A

The enzyme that is activated by a rise in cAMP

A serine/threonine kinase

Activates other enzymes/channels to generate the cell’s response

Receptor Density

An increase in this would lead to an increased level of receptor binding

A decrease in this would lead to a decreased level of receptor binding

Serine/Threonine Kinase

An enzyme that causes a conformational shift (change in shape) in a protein that leads to activation of function, like turning on an enzyme, through phosphorylation

STAT

A transcription factor

Phosphorylated in the JAK signaling pathway allowing this to dimerize, translocate to the nucleus, and increase transcription of specific messages

Affinity

The strength w/ which a chem messenger binds to its receptor

Describes the physical attraction between hormone and receptor binding site

If this is higher, a curve will form further on the left

Gi

Decreases adenylate cyclase activity inhibiting it

Arachadonic Acid

A molecule produced when phospholipase A2 acts on membrane phospholipids

When broken down, produces:

• Prostaglandins

• Leukotrienes

• Thromboxanes

Phospholipase C

The enzyme that breaks PIP2 into IP3 and DAG

Activated by the Alpha subunit of Gq

Tyrosine Kinase

The type of enzyme that creates a docking site when it attaches phosphate groups to specific amino acids in a peptide

Causes autophosphorylation

Proteins will bind to this when phosphorylated to become phosphorylated themselves, making this receptor also function as an enzyme

Inositol Triphosphate (IP3)

Binds and opens receptors that are Ca2+ channels in the ER of the cell

Transduction

The process of changing 1 signal, such as chemical messenger concentration or light energy or sound energy, into a different signal, such as activated enzymes or opened ion channels to change membrane potential

Estrogen Response Element

The sequence of nucleotides in a chromosome that an activated (bound) estrogen receptor would bind

NSAIDs

Reduce prostaglandin formation by blocking or reducing the activity of cyclooxygenase enzymes

Block COX enzymes as well

Alpha subunit of Gs

Activates adenylyl (adenylate) cyclase

AKA “The Catalytic Subunit”

Calcium Pumps

Located on both the cell membrane and ER

Reduces activity along signaling pathways when chemical messengers no longer activate the receptors

Janus Kinase (JAK)

A signal transduction pathway involving the phosphorylation of the transcription factor STAT allowing it to dimerize, translocate to the nucleus, and increase transcription of specific messages

G Proteins

A GTPase that binds and breaks down GTP

Protein Kinase C

Activated to produce eicosanoids

Activated by depolarization of the cell membrane potential (such as by Calmodulin)

BetaGamma Subunits

Subunits of receptor-activated G proteins that is sometimes referred to as the “regulatory” subunit

Sigmoidal Curve

Generated when graphing the binding of a ligand from 0 - 100% binding as a function of the concentration of available ligand

Calmodulin

A common cytosolic protein that is frequently bound and activated by Ca

Depolarizes the membrane potential to activate Protein Kinase C (working with DAG)

Upregulation

An increase in the total # of target-cell receptors for a given messenger

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

Refers to when receptors increase in density due to very little binding by its natural ligand

Caused by constant low levels of the hormone that binds to the receptor

Downregulation

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

May occur in response to chronic high extracellular concentration of the messenger

Refers to when receptors decrease in density du to too much binding by its natural ligand

Caused by constant high levels of the hormone that binds to the receptor

Saturation

The degree to which receptors are occupied by messengers

Describes the max response and binding possible for a receptor

Adenylyl (Adenylate) Cyclase

Activated by Gs

The enzyme that breaks ATP down to form cAMP

Amplification

The purpose and importance of a series of activated enzymes in a signaling pathway

Specificity

The ability of a receptor to bind only 1 type or a limited # of structurally related types of chem messengers

Describes the power of the connection between a ligand and a receptor

Governed by the 3D shape of both the ligand and the receptor (Affinity) and the alignment of the charged and uncharged areas of both molecules

Steroids

Reduce Prostaglandin formation by blocking/reducing the activity of Phospholipase A2, which inhibits arachidonic acid formation

Blocks many inflammatory/immune pathways

Eicosanoids

Lipid soluble chem messengers produced by Protein Kinase C to help trigger/stimulate inflammatory processes in an area of injured tissue:

• Leukotrienes

• Prostaglandins

• Thromboxanes

Leukotrienes

An eicosanoid that helps regulate immune system activity

Attracts and stimulates formation of WBCs

G Protein Coupled Receptors (GCPRs)

The largest superfamily of receptors/signaling systems

Pathway:

1. Chem messenger binds to receptor

2. Receptor changes conformation, affecting the conformation of attached G Protein

3. Old GDP unbinds and new GTP binds from the cytosol

4. Alpha subunit dissociates and activates an effector protein

Effector proteins are often enzymes

Receptor always bonds to leftover G protein from last time

Activation may include:

• Ion channels

• Phosphorylation

• Enzyme activation

• Transcription regulation

Gs

Activates adenylate cyclase to increase its activity

Ependymal Cells

Glial cells that line the tube/cavity of the CNS and produce/keep in CSF

Relative Refractoriness

Some of the voltage-gated Na+ channels are in their initial state and some are still inactivated

With a very strong stimulus, “small” action potentials can be generated w/ diminished amplitude

Oligodendrocytes

Glial cells that make the myelin sheaths in the CNS

Action Potential

A brief all or none depolarization of the membrane, which reverses polarity in neurons and has a threshold and refractory period and is conducted w/o decrement

Generated by large changes in current flow across the membrane of axons

Current flow for more than 1 ion changes during this event

Shows the same amplitude as it travels (all or none)

Travels slowest and only on axons

Activated by:

• Receptor Potential

• Post-synaptic Potential

• Pacemaker Potential

Propagated fastest by fat and myelinated axons and self-propagated by the spread of currents to depolarize an adjacent area of membrane over threshold

Fired by the positive feedback loop of voltage-gated Na+ channels

Features:

• All or none: once the membrane is depolarized to threshold, amplitude is independent of the size of the initiating event

• Cannot be summed

• Has a threshold that is usually about 15 mV depolarized relative to the resting potential

• Has a refractory period

• Is conducted w/o decrement and the depolarization is amplified to a constant value at each point along the membrane

• Duration is constant for a given cell type under constant conditions

• Is only a depolarization

• Initiated by a Graded Potential

• Mechanism depends on voltage-gated ion channels

K+

The ion that has the highest concentration w/in the cell and what the cell membrane is most permeable to at rest

Has a negative equilibrium potential

Retrograde Transport

Transport from the nerve terminals to the soma of a neuron

Na+

The ion w/ the highest concentration outside the cell

Has the most positive equilibrium potential

Axons

The larger the diameter means that the current of graded potentials travels faster w/ less decrement, thus firing an Action Potential simultaneously in a larger segment of this at one time

The nerve fiber of the neuron that carries outputs to target cells, sometimes over great distances

Divided into the hillock and terminals

Peptides and Proteins

Negatively charged molecules that are largely retained w/in the cell, thus contributing to the net negative charge of resting membrane protential

Goldman Equation

A weighted, composite version of the equation for equilibrium potential of all the ions affecting membrane potential

Weighted w/in its own formula for the membrane permeability for each individual ion

35

The age at which Myelin sheaths stop thickening

Nernst Potential

When the voltage across the membrane at the point where an ion currents across the cell membrane in both directions are equal

Describes all the forces generating Ex for a particular ion (x)

Ex is about = (61/Z)logCo/Ci

• Ex is equilibrium potential for ion x in mV

• Ci is intracellular concentration of x in mM

• Co is extracellular concentration of x in mM

• Z is the valence of the ion

Graded Potential

A potential change of variable amplitude and duration that is conducted decremental and has no threshold or refractory period

The flow of current w/in nerve cells generated by chemically-gated channels

Travels fastest through the cell, but loses energy as it travels, showing decrement

Travel on the dendrites and soma

Generated by depolarization via Nicotinic Cholinergic Channels that open after a neurotransmitter binds them

Small, variable changes in membrane potential of the Soma and Dendrites that add up to determine whether or not the axon will fire an Action Potential along its axon

Features:

• Amplitude varies w/ size of the initiating event

• Can be summed

• Has no threshold

• Has no refractory period

• Amplitude decreases w/ distance

• Duration varies w/ initiating conditions

• Can be a depolarization or a hyperpolarization

• Initiated by environmental stimulus (receptor), neurotransmitter (synapse), or spontaneously

• Mechanism depends on ligand-gated ion channels or other chemical/physical changes

Repolarization

A phase of the Action Potential associated w/

• Increased K permeability

• Decreased Na permeability

Absolute Refractoriness

When the voltage gated Na+ channels are all closed and inactivated in the membrane of an axon or muscle cell and none of the Na+ channels have reset

No action potentials can occur no matter how strong the stimulus

Ends via the negative feedback loop of voltage-gated K+ channels

Kinesin

The molecular motor that carries vesicles from the soma of a neuron to the nerve terminals

Acts in Anterograde Transport

Interneurons

The type of neurons that are found in the CNS and the most abundant neurons in the body

Connect between other neurons

Synaptic Cleft

The space between the nerve and muscle cell membrane at the neuromuscular junction

Efferent Neurons

Motor Neurons, sends signals out of the CNS

There are 2 in sequence, conveying CNS signals to autonomic nervous system/effectors

Membrane Capacitance

The collection of oppositely charged particles on either side of the cell membrane due to RMP

Microglia

The glial cells which function as immune cells w/in the CNS

Dynein

The molecular motor that carries vesicles from the nerve terminals of a neuron to its soma

Acts in Retrograde Transport

Saltatory Conduction

Happens down myelinated axons

The signal under the myelin is current inside the cell and the signal at the nodes is an Action Potential

Satellite Cells

Glial cells that help provide nutrients for and communicates w/ neurons in ganglia in the PNS and also forms the BBB

Synaptic Plasticity

The ability to make and maintain new synapses as well as the ability to modify synaptic strength

Somatic Nervous System

The division of the nervous system that controls skeletal muscle movement

Salutatory Propagation

Happens down the axon

Currents carry graded potentials under the myelin sheath, and action potentials occur at the nodes of Ranvier

1. Graded Potentials travel through myelinated areas by local current flow much faster than Action Potentials

2. Action Potentials only occur at Nodes of Ranvier and jump from node to node, proceeding down the axon faster than usual

Retrograde Transport

The movement of a vesicle of materials from the nerve terminals to the soma by the aid of Dynein

Herpes if famous for following this back into the cell to hide from the immune system

Anterograde Transport

The movement of a vesicle of materials from the soma to the nerve terminals via Kinesins

Schwann Cells

The glial cells which produce the myelin w/in the PNS

Afferent Nerve

Sensory Nerve, sends signals to the CNS

Rising Phase of Action Potential

Caused by the opening of voltage-gated Na channels

Falling phase of Action Potential

Caused by both the closing of voltage-gated Na channels and the opening of voltage-gated K channels

Astrocytes

The glial cells which help form the BBB and provide neurons w/ nutrients from blood for the CNS

Depolarizing Phase of Action Potential

Increased Na permeability

Tonicity

The movement of water in/out of cells

Only solutions possess this

Hypotonic

Water moves into cell to cause swelling or lysing

Lower osmolarity than cytosol

Isotonic

No net movement of water

Equal osmolarity to cytosol

Hypertonic

Water moves out of cell, shrinking it

Higher osmolarity than cytosol

Osmolarity

The sum of molarities of all particles in a solution

A pulling, negative force

Note:

• Each ion of an ionic compound counts separately (1 mol NaOH is 3 Osmols: Na+, O-, and H+)

• Covalently bonded compounds will not separate and will count as a single particle (1 mol Glucose is 1 Osmol glucose)

300 mOsm

The standard osmolarity for a normal cell

Membrane Receptor

Made up of 2 domains:

1. Extracellular binding domain

2. Intracellular signaling/transducing domain

Intracellular Receptors

Proteins in the nucleus or cytosol, but all eventually end up in the nucleus

Once bound to its hormone, becomes a transcription regulator that may or may not be always active

Nuclear or cytosolic, bound or unbound when free

Respond to mostly lipid soluble molecules because they are thought to pass through the membrane. Hormones/Cytokines require specific transport proteins (Globulin) to enter the cell

Response Lements

Small parts of promoters or enhancers in the regulatory regions of a gene

Bind to Intracellular Receptors to make them Transcription Regulators

N-terminal Domain

The domain of an intracellular receptor that participates in gene activation

DNA-binding Domain (DBD)

The domain of an intracellular receptor that has subtle differences in structure to determine which segments of DNA are bound by different receptors

Hinge Domain

The domain of an intracellular receptor that is required for nuclear receptors to localize in a cell nucleus

Ligand-binding Domain (LBD)

The domain of an intracellular receptor that has differences in shape to determine which messenger binds to a given receptor

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

Ex. Decongestants

Receptor

A specific protein in either the plasma membrane or the interior of a target cell that a chem messenger binds w/, thereby invoking a biologically relevant response in that cell

Competition

The ability of different molecules to compete w/ a ligand for binding to its receptor

Participants generally are similar in structure to the natural ligand

Antagonist

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

Therefore, prevents the actions of the natural ligand

Ex. Antihistamines

Increased Sensitivity

The increased responsiveness of a target cell to a given messenger

May result from Upregulation of receptors

Kinases

Enzymes that phosphorylate using ATP

Serines change the steriochem of enzyme

Tyrosines act as a binding site for something to bind, like P

Transcription Factors

AKA Transcription Regulators

Small molecules, generally peptides, that help to form transcription regulatory complexes that function to promote or repress transcription

Docking Protein

A protein that interacts w/ a phosphorylated Tyrosine Kinase, a receptor that also acts as an enzyme, to become phosphorylated itself and form a binding site to interact w/ other molecules

JAK-STAT Family Receptors (Cytokine Receptor Family)

1. JAK binds to the receptor after the receptor receives its messenger, which then activates JAK

2. Activated JAK phosphorylates Tyrosine on STAT

3. Phosphorylated STATs dimerize (bind to each other)

4. Binds to DNA at response elements to regulate Transcription

Effector Proteins

Proteins that cause important actions inside the cell after activation of a signaling pathway

Often activated by GPCRs

After activation, causes a rise in Second Messengers

Second Messengers

Increase in levels after an Effector Protein is activated

Ex.

• cAMP (Cyclic 3’,5’-adenosine monophosphate)

• cGMP (Cyclic 3’,5’-guanine monophosphate)

• DAG (Diacylglycerol)

• IP3 (Inositol triphosphate)

• Ca2+

• Arachidonic Acid

Cytosol levels are always being reduced via enzymatic degradation and Ca2+ pumps

cAMP Pathway

A pathway activated by Epinephrine

Pathway:

1. Ligand binds to a G protein receptor

2. GDP moves out and GTP moves into the alpha subunit

3. Alpha subunit binds to Adenylyl Cyclase

4. Adenylyl Cyclase activates and converts ATP into cAMP

5. cAMP activates Protein Kinase A

6. Protein Kinase A activates other enzymes/channels

7. Phosphodiesterase degrades cAMP into AMP

Can result in many different things:

• Active transport

• Opening ion channels

• Protein synthesis/Ca2+ transport in the ER

• Converting DNA into mRNA in the nucleus

• Activating an enzyme to break down glycogen

• Activating an enzyme to break down lipids

• Causing transport, secretion, or changes in cell shape via Microtubules

Phospholipase C, DAG, and IP3 Pathway

Pathway:

1. Alpha subunit binds and activates Phospholipase C

2. PLC breaks PIP2 into IP3 and DAG

3. IP3 binds to ER receptor opening Ca2+ channel

4. Ca2+ and DAG activate Protein Kinase C

5. Protein Kinase C can then phosphorylate several different proteins to affect function

Calcium-Calmodulin Pathway

Pathway:

1. Ca2+ rises in cell

2. Ca2+ binds Calmodulin

3. Activated Ca2+-Calmodulin binds and activates CAMKs

4. Phosphorylation via serine/threonine kinase activity

5. Can lead to membrane depolarization, triggering secretion of vesicles of neurotransmitters/hormones, direction activation of ion channels/enzymes (rarely), and binding of Ca to Calmodulin (commonly)

Increasing Calcium

Pathway:

1. Plasma membrane Ca2+ channels open in response to a first messenger

2. Ca2+ is released from ER, mediated by IP3

3. Active Ca2+ transport out of the cell is inhibited by a second messenger

or

1. Opening of voltage-gated Ca2+ channels

Prostaglandins

Eicosanoids that are involved in smooth muscle contraction

Formation blocked by NSAIDs

Thromboxanes

Eicosanoids that are involved in clotting pathways

Endocrine System

Organ system that does the following:

• Hormones released to affect distant target cells

• Coordinates responses over time course of a few seconds to months