M&C Exam 3 - General

Action Potential

Caused by depolarization (more positive electrical potential) in excitable cells - short lasting. Depolarization occurs when Na+ enters the cell, hyperpolarization (more negative electrical potential) occurs when K+ leaves.

Antiporter

use the concentration gradient in this same manner but transport in the opposite direction

ATPase Pump

enzyme that catalyzes the hydrolysis of ATP into ADP and phosphate, allowing for active diffusion up the concentration gradient (ion pumps)

Channelopathies

Mutation of an ion channel usually caused by gain of function mutations from enhanced activation or impaired inactivation of ion channels

Channel Blockers

substances that inhibit ion channels, affecting nerve and muscle function.

Ligand Gated Channels

Activated by binding of a chemical ligand to the channel (Ex. neurotransmitters like glutamate, acetylcholine, ATP, etc.)

Nociceptor/Sensory Receptor

Receptor that responds to potentially damaging stimuli by sending signals to the spinal cord and brain

Passive Diffusion

Movement of ions from a high concentration to a low concentration - (down the concentration gradient)

Resting Potential

Difference in electrical potential between the inside and outside of the cell at rest (~-70mV - more negative inside) - High K+ on inside, and high Na+ on outside!

Symporter

Transport anions down their concentration gradient to fuel the transport of another type of ion in the same direction

Transient Receptor Potential Channels

Interact with high threshold transducer channels which sense damaging mechanical, thermal and chemical stimuli and translate them into electrical signals - don’t share a lot of homology with each other (good drug targets!)

Uniporter

transport of a single ion down it’s concentration gradient

Voltage Gated Channel

Open when the cell is depolarized (short action). Uses the mechanism of membrane excitability and is selective for Na, K, or Ca.

Membrane Potential

the difference in electrical potential between the interior and the exterior of a cell

Patch Clamp

Experimental method to study the membrane potential of a cell. Clamp allows the scientist to set a specific voltage/current to study the changes of the membrane potential.

Thyroid hypersecretion

A type of channelopathy that is caused autoantibodies activating the thyrotropin receptors (acting as an agonist)

Epilepsy

A type of channelopathy that is caused autoantibodies activating the glutamate receptors (acting as an agonist)

Nuclear Receptor

Superfamily of ligand-activated transcription factors that control development, differentiation, and homeostasis through sensing metabolic intermediates and activity.

Glucocorticoid Receptor

Type 1 nuclear receptor (Steroid) that resides in the cytoplasm and translocates to the nucleus upon activation

Thyroid Hormone Receptor

Type 2 nuclear receptor (non-steroid) that resides in the nucleus - can act as a repressor of transcription by binding to DNA in inactive state

Hormone Response Elements

Specific DNA enhancer sequences located in the promoter region of a target gene that are recognized and bound by steroid NRs

Nuclear Receptor Regulation

• Ligand dependent transcription (classic)

• Active repression

  • Dimer of receptors without ligand (REPRESSES)

• Coactivation

  • transcription factors bind directly to DNA, then receptors bind to transcription factors

• Corepression

  • Transcription factors block nuclear receptor binding

Active repression (nuclear receptor regulation)

Dimer of receptors without ligand binds to DNA, repressing it

Coactivation (nuclear receptor regulation)

transcription factors bind directly to DNA, then receptors bind to transcription factors (ex. STATs bind then Glucocorticoid repectors)

Corepression (nuclear receptor regulation)

transcription factors block nuclear receptor binding, leading to repression

Enzyme 5-alpha reductase

Required for the conversion of androgen precursors to dihydrotestosterone, which has a potent agonist effect on the androgen receptor

PPAR-alpha

Type 2 NR that directly regulates a network of genes encoding the proteins required for the uptake of fatty acids, enzymes req. for beta-oxidation, and ketogenesis by binding to control regions in the promotor of these genes - activation promotes utilizing fat as an energy source

PPAR-gamma

Type 2 NR that has opposing functions in the regulation of fat metabolism - the master transcription regulator of adipogenesis and promotes lipid storage

Androgen

Actions similar to testosterone used for hormone therapy 

Prostaglandin E2

Key mediator of immunopathology in chronic infections and cancer through mediation of anti-inflammation and angiogenesis responses

Prostaglandin G2

Produced from arachidonic acid via the cyclooxygenase pathway

Prostaglandin I2

Housekeeping prostainoid for endothelial, vascular and mucosal integrity, produced by prostaglandin synthases

Prostaglandin D2

Prostanoid that mediates anti-inflammatory response, produced by prostaglandin synthases

COX-1

Constitutively expressed, needed for the synthesis of prostaglandin and thromboxane in many types of cells (GI and blood platelets)

COX-2

Inducible, has a major role in prostaglandin biosynthesis in inflammatory cells and in the CNS

Arachidonic acid

Made through the degradation of phosphatidylcholine by phospholipase A2 - mainly metabolized through the lipoxygenase pathway to make leukotrienes, and the cyclooxygenase pathway to make prostaglandins and thromboxane

1st Clinical Gene Therapy Test

Correcting the adenosine deaminase (ADA) gene by transferring the missing gene into isolated lymphocytes of patients with SCID using an ex-vivo gene transfer

Ex vivo cell mediated targeting

Cells (e.g., stem cells or immune cells) are
removed from the patient, cells are manipulated
outside the body to take up the DNA and then cells are put
back into the patient

In vivo direct targeting

Therapeutic gene is packaged into a vector and directly injected into the patient

Gene replacement

Gives the cells a new, functional copy of the missing or nonworking gene - most FDA gene therapies use this strategy

Gene editing

Inserts, removes, changes, or replaces exisiting DNA at precise spots along the gene, where the goal is to change the existing gene and correct mutations where they occur (CRISPR)

CAR-T

Involves changing a person’s own immune cells to recognize and fight cancer cells inside the body - incorporates gene-replacement therapy, as these cells resulted from ex vivo cell mediated gene targeting

RNAi

Includes siRNA, shRNA, and miRNA, but all rely on a dicer and lead to the cleavage of mRNA

Optogenetics

Control of neuronal activity in living tissue using light pulses (retinal gene therapy)

Ca Voltage Gated Channels

Distinct subtypes (L, T, N, P/Q, and R) that vary in respect to their activation and inactivation kinetics, voltage threshold, conductance, and sensitivity to blocking agents.

Ca Release Channel

Present on the ER or SR instead of the plasma membrane, and control the release of Ca+ from intracellular stores through IP3 and Ryanodine receptors

Store Operated Calcium Channels (SOCs)

Located on the plasma membrane - allows Ca+ entry into the cell via an interaction with a Ca+ sensor protein from the ER membrane with the Ca+ channel in the plasma membrane (respond to GPCRs that elicit Ca+ release, allowing Ca+ to remain elevated when stores are low)

DNA Binding Domain

Highly conserved region of a NR that contains 8 Cys residues and 2 Zn+ ions that form a Zinc Finger

Ligand Binding Domain

Part of the NR that recognizes the hormone and is formed by direct repeats or inverted repeats

Thromboxanes

Lipid mediators produced by arachidonic acid in platelets through the prostaglandin pathway that play a role blood clotting (thrombosis) and vasoconstriction

Integrins

Proteins on the cell surface that function as transmembrane receptors, connecting the cell’s internal cytoskeleton to the EC matrix or other cells - allow immune cells to move through the blood vessels

Leukotrienes

Lipid mediators produced by arachidonic acid in immune cells through the lipoxygenase pathway that play a role in inflammatory responses

Eicosanoids/Prostanoids

Broad term for the molecules derived from arachidonic acid (prostaglandins, leukotrienes, and thromboxanes)