23-11-21 - Ion Channels Flashcards
What are 4 examples of factors that opens ion channels?
What are examples of each?
- Voltage
- Changing membrane voltage in depolarizing or hyperpolarizing direction
- E.g voltage-gated Na+ or K+ channels
- Ligands
- Neurotransmitters binds to the extracellular part of the channel and causes a conformation shape change in the ion channel, causing it to activate and open
- E.g glutamate receptor
- A 2nd messenger can also bind at the cytosolic surface and activate the channel
- E.g Calcium binding to intracellular ryanodine receptor
- Stretch
* E.g mechanosensitive channels - Light
* R.g channel rhodopsin
What is channel gating?
What can be done with raw data from observation of channel gating?
What gating properties can we look into?
How can this be calculated?
- Channel gating refers to the opening or closing of ion channels
- With raw data of channel gating, a 50% threshold can be set, where if the current is above this point, the channel is considered open
- By establishing an open and closed state, we are idolizing the data, which allows us to look into the gating properties of channels => modeling the data by simplifying real-world, often noisy experimental observations into discrete open and closed states
- We can look into how long the gate is in an open and closed state, the amplitude of opening current, and the probability of the channel being open
What is Ohms law?
What is single channel conductance?
How can it be calculated?
Why does this allow conductance to be calculated?
Why is calculating conductance important?
- Signal channel conductance is a measure of how good a channel is at letting current run through it
- Conductance can be calculated by measuring the current running across a channel at different voltages and plotting a graph of current against voltage, where resistance is equal to the gradient (V=IR – Ohms law)
- Resistance (Ohms) is equal to 1/g, with g being conductance (unit is siemens – S)
- This allows conductance to be calculated as channels act as resistors.
- When they are closed they prevent anything from moving through
- When they aare open, this allows for conductance as ions can move through from one side of the membrane to the other
- => When a channel is closed, it blocks ions from passing through, so there’s no current or conductance.
When the channel is open, ions can flow, and the channel allows conductance. - Calculating conductance is important as it gives us an important understanding of role of channels
What is macroscopic current?
How is it calculated?
- Macroscopic current (I) is the whole cell current
- It is calculated by finding the product of the number of channel in the membrane area (N), the unitary current (current through an ion channel - i) and the probability of the channel opening (Po)
What are ion channels selective to?
What are inhibitors of the Na+ and K+ ion channels?
- Ions channels are selective to the ions that pass through them (ion selectivity)
- Tetrodotoxin is an inhibitor the Na+ channels
- Tetraethylammonium is an inhibitor for K+ channels
What is the sarcoplasmic reticulum?
What is its purpose?
What 2 receptors are present on its surface?
What are the concentrations of calcium outside the cell, inside the cytoplasm, and inside the sarcoplasmic reticulum?
What is an example of another calcium channel in the cell?
What 2 things is homeostasis of calcium concentration important for?
What 2 things can dysregulation of calcium homeostasis cause?
- The Sarcoplasmic reticulum is a specialized form of endoplasmic reticulum that is found in most cells
- The sarcoplasmic reticulum acts as a calcium storage in muscle cells
- On its surface, there are Ryanodine receptor and IP3 calcium channels
- Outside the cell Ca2+ concentration is 1mM, in the cytoplasm it is 100nM, inside the SR it is 1mM (millimolar)
- There is also TPC2 calcium channel on the lysosome of the cell
- Homeostasis of calcium concentration is important for heartbeat and muscle contraction
- Dysregulation of homeostasis of calcium concentration can cause pathology, such as cardiac arrhythmias and malignant hyperthermia
Describe 8 the steps of the cardiac excitation-contraction coupling.
What occurs to return this cycle back to the start?
How can arrhythmias and heart failure be caused by this cardiac cycle?
- Cardiac action potential depolarised the plasma membrane
- This depolarisation activates voltage gated calcium channels on the plasma membrane
- Calcium flows down its concentration gradient from outside of the cardiac cell into the cell
- The calcium concentration is not high enough to cause a cardiac contraction by itself
- Calcium binds to Ryanodine 2 Receptor (RYR2 most common in cardiac muscle) on the sarcoplasmic reticulum as a ligand
- Through a process called calcium induced calcium release, the calcium activates the cardiac ryanodine receptor
- This causes calcium to flow down its concentration gradient from the sarcoplasmic reticulum into the cytoplasm of the cell
- Calcium can then bind to contractive machinery and stimulate contraction
- When we want the heart cells to relax, calcium is taken back up into the sarcoplasmic reticulum stores via a Calcium ATPase called SERCA, or it can be extruded from the cell by a calcium exchanger
- This returns calcium concentration to resting levels
- If there is inappropriate release of calcium from the stores in the sarcoplasmic reticulum, this can lead to arrhythmias
- If these stores become depleted, this can cause heart failure, due to weakened contraction
What is Ryanodine Receptor (RyR)?
What is The RyR regulated by?
How can disease be caused by the RyR?
- The RyR is an example of a macromolecular complex
- It is regulated by many different binding components e.g kinases, phosphatases, binding proteins
- It is found in diseases, there is change in these binding partners e.g excess phosphorylation, absence or altered function of binding partners
- This leads to altered function of the Ryanodine Receptor, which causes disease
What are channelopathies?
What is CPVT?
What are 3 symptoms of CPVT?
Why is CPVT difficult to diagnose?
How many mutations are associated with CPVT?
Here’s a clearer version of your text with improved flow and readability:
Channelopathies are diseases caused by defects in ion channels, which may result from genetic mutations or acquired factors.
Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT) is an inherited autosomal dominant channelopathy linked to mutations in the ryanodine receptor (RyR2).
Symptoms of CPVT include:
- Dizzy spells
- Fainting episodes
- Sudden cardiac death
CPVT-related arrhythmias occur due to dysregulation of the RyR2, leading to excessive calcium release from the sarcoplasmic reticulum. This calcium overload disrupts normal cardiac rhythm.
Diagnosing CPVT can be challenging because its characteristic ventricular arrhythmias typically appear only during physical stress or exercise, when adrenaline levels rise.
So far, 69 point mutations in the RyR2 gene have been identified in patients with CPVT (specifically CPVT1).
Let me know if you’d like to further refine it or add more details!
Describe the 4 steps of the skeletal muscle excitation-contraction coupling
Here’s a simplified version of the explanation:
Ryanodine Receptor 1 (RyR1) is mainly found in skeletal muscles and helps control muscle contraction. It gets activated through a direct interaction with a nearby channel called the voltage-gated calcium channel (LTCC).
When the LTCC is triggered, it causes a shape change in RyR1, turning it on. This activation opens RyR1, allowing calcium to flow out of the sarcoplasmic reticulum (SR), where calcium is stored, into the main part of the muscle cell.
The calcium then binds to the muscle’s contractile machinery, which triggers the muscle to contract.
Would you like me to elaborate on any part?
What is malignant hyperthermia associated with?
What type of disorder is it?
What does it lead to a sever reaction to?
Where does it first manifest?
What is the underlying mechanism of MH?
What are 4 symptoms of MH?
What is administered prior to surgery to treat MH?
Here’s a clearer version of the explanation:
Malignant Hyperthermia (MH) is a pharmocogenetic disorder affecting skeletal muscle that causes a dangerous reaction to certain anesthetics and muscle relaxants. It is linked to mutations in the Ryanodine Receptor Type 1 (RyR1).
Key Facts About MH:
- Trigger: MH occurs during surgery after exposure to specific anesthetics or depolarizing muscle relaxants.
- Cause: Mutations in the RyR1 gene make the receptor overly active. When exposed to these drugs, RyR1 releases too much calcium into the muscle cells.
- Effects: This calcium overload leads to excessive muscle activity and energy use, causing a series of severe symptoms.
Symptoms of MH:
- Muscle rigidity (stiffness)
- High fever
- Increased acid levels in the blood and tissues (acidosis)
- Rapid heart rate
Treatment:
- Dantrolene, a postsynaptic muscle relaxant, is used to treat MH. It works by blocking the RyR1 receptors, reducing calcium release, and restoring normal calcium levels in the muscle cells.
Early treatment is critical, as MH can be fatal if not addressed promptly.
Let me know if you’d like further adjustments or additions!
