Midterm 4 Flashcards by Adam Robichaud

What type of protein allows ion channels to function?
a. Ion transporters
b. Calcium signal
c. Glycolysis
d. Neurotransmission

A. Ion transporter (against the concentration gradient)

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What determines the membrane potential?

Concentration of ions

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What three things are responsible for ion movement across a membrane?

Channel permeability, charge, and concentration gradient

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How do you measure levels of calcium in a cell?

Using calcium sensitive dyes such as Rhod-2 or Fluo-4.
Or calmodulin-GFP

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Where is calcium concentrated at the cellular level?

Outside the cell

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What are the major types of Calcium permeable ion channels?

Non-selective cation channels (TRP)
Ligand-gated (glutamate, ACh)
Intracellular Ca release channels
Voltage dependent Ca Channels

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What is the main internal calcium source?

The endoplasmic reticulum

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What features make calcium an ideal messenger?
a. Low intracellular concentrations at rest
b. Ability to create rapid on/off signal
c. Many proteins are calcium sensitive
d. A and B
e. A, B, and C

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What is the primary method of coupling electrical activity to Calcium signaling?

Voltage gated calcium channels (increased activity with membrane depolarization)

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How does polarization affect calcium signaling?

Depolarization: Increased signaling

Hyperpolarization: Decreased signaling

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What are the subunits of a voltage-dependent calcium channel?

⍺1 - pore forming unit
Acessory: ß, ⍺2-δ, 𝛾, calmodulin

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What is the molecular target of pregabalin and gabapentin and what do they treat?

⍺2-δ subunits on Voltage dependent calcium channels. Treats neuropathic pain

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The diabetes drug, glibenclamide, inhibits potassium channels to
depolarize pancreatic beta cells. What effect will this have on the
beta cell?

A. Increase Ca
B. Decrease Ca
C. No change because it is a potassium channel
D. Increase contractility

A (depolarization = increased Ca)

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What is the function of the beta subunits on VDCCs?

Speed up the rate of VDCC activation, influence drug binding

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What is the function of the 𝛾 subunit on VDCCs

Regulatory function to decrease a channel currents

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True or False
Calcium channel inhibitors only interact with the pore forming
alpha-1 subunit of VDCCs?
A. True
B. False

False; There are many classes of VDCC inhibitors that interact with different parts of the channel

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True or False
All calcium channels are voltage dependent and can only be
found in excitable tissues?
A. True
B. False

False, many other types of Ca channels

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Where are L-type VDCCs located primarily?

The cardiovascular system

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What is the physiological effect of Ca channel blockers?

Decreased peripheral resistance to decrease blood pressure
Dilate coronary arteries to increase cardiac oxygen supply

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What are the general targets for the different Ca channel blockers?

Dihydropyridines: Vascular potency > Myocardial suppression

Phenylalkylamines and Benzothiazepines: Vascular:cardiac ~ 1:1

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What conditions do Ca channel blockers treat?

Hypertension, Angina, Arrythmias

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What is the function of ryanodine receptors?

To release calcium from the ER into the cytoplasm

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What is the general structure of Ryanodine Receptors (RyRs)

Homotetramer (550-660 kDa)

N-terminus: Cytoplasmic
C-terminus: Pore forming domain

How much faster can ryanodine receptors conduct Calcium than L-type channels?

50X

Where are the three RyR subtypes most commonly found?

RyR1: Skeletal muscle RyR2: Cardiac Muscle RyR3: Brain

How does L-type VDCCs and RyRs interact in skeletal muscle?

Activation of VDCCs leads to mechanical opening of ryanodine, leading to contraction

What are some diseases associated with RyR mutation?

Malignant Hyperthermia Central Core disease Polymorphic ventricular tachycardia

How does IP3 modulate IP3 receptors?

IP3 disables the feedback inhibition that higher levels of calcium normally exhibit on the channel

How many transmembrane domains do IP3 receptor subunits have

What is the structure of an IP3R channel?

Tetramer

Where are the IP3R subtypes primarily expressed?

IP3R1: neurons IP3R2: Hepatocytes IP3R3: Epithelial cells (rapidly proliferating)

How does ATP effect the activation curve of an IP3R

Shifts to the left

What are the two major classes of extracellular matrix?

Glycoaminoglycans Fibrous / Adhesive proteins - add tensile strength and elasticity to ECM

Structure of collagen

Triple helix of alpha chains

What are the four common amino acids in collagen

Pro, Gly, HO-Pro, HO-Lys

What are the three types of collagen?

Fibrillar Fibril - associated Network forming

What is the role of fibrillar collagen?

Tension-bearing structures, Arranged according to tissue function Mutations = osteogenesis imperfecta

What is the major function of fibril-associated collagen

mediates fibril-fibril and fibril-ECM interactions

What is the major function of network forming collagen?

Flexibility

What is fibrinogen?

Soluble protein found in the blood, converted by thrombin to fibrin ==> blood clot

What are the most prominent ECM drug targets?

Lymphocyte integrins and platelet integrins

What can targeted antibody therapeutics treat?

Acute coronary indications Multiple Sclerosis Chron's Disease

What are the advantages / disadvantages of targeted antibodies

A: High specificity and affinity D: High cost of treatment

What are the advantages / disadvantages of peptidomimetics?

A: Modeling design is easy, natures choice D: Very low specificity

What are the advantages / disadvantages of small molecule drugs (ECM)

A: Good drug / pharmacokinetic properties D: Don't work well

What effects do integrin drugs exert?

Anti-thrombotic and anti-inflammatory effects

What was the first approved anti-platelet integrin drug?

Reopro (abciximab)

What are the two destinations for blood pumped from the heart?

Lungs (right ventricle) and systemic circulation (left ventricle)

What are the types of muscle?

Smooth (intestines, bladder, uterus, blood vessels) Striated muscle (cardiac, skeletal)

In order from outside to inside, name the layers of a blood vessel

Adventitia Tunica Media Tunica intima

What is a major difference in the structure between arteries and veins?

Arteries have a thicker layer of smooth muscle used to contract and push blood

Why can smooth muscle contract tonically for long periods of time?

Slow cross-bridge formation, low energy requirement, high force of contraction

What are some things that control vascular tone?

Extrinsic: Neural and hormonal signaling Intrinsic: metabolites, hormones, endothelial factors

What are the three hormonal systems that regulate vessel tone?

Renin-angiotensin system Antidiuretic hormone Adrenaline