Calcium Homeostasis 2 Flashcards
What activates the ryanodine receptor
Calcium - when high calcium conc is cytoplasm this opens the ryanodine receptor to trigger more calcium release from cytoplasmic reticulum and increase the cytosolic calcium
Where is the ryanodine receptor mostly found
Cardiac and muscle cells
How does an action potential trigger the ryanodine receptor to open
AP –> voltage-gated calcium channels open in T tubule of cell membrane –> T-tubule interacts directly with ryanodine receptor in ER/SR –> Opening of Ryr-sensitive calcium release channels –> calcium release into cytoplasm
Essentially a positive feedback mechanism as initiated by calcium and increases calcium
What happens when calcium levels get too high (mM conc)
This inactivates RyR so the signal is turned off - a protective mechanism to prevent extremely high calcium levels
What is the ryanodine receptor similar to
IP3R - tetramer and large with a central pour.
Ryanodine twice as big though
What effect does ryanodine have on the ryanodine receptor and what is important about this
Low conc - permanently open but subconductance state
High conc - fully block channel
THIS IS NOT PHYSIOLOGICAL
Where is ryanodine receptors important
Malignant hyperthermia
Give some features of malignant hyperthermia
Inherited disorder - 1 in 15,000
Caused by volatile anaesthetic (halothane)
Due to defect in RYR1 calcium channel release - causes increase sensitivity to caffeine and calcium and greater channel conductance and longer opening times of channels
What is the pathophysiology of malignant hyperthermia
Uncontrolled increase in sarcoplasmic reticulum calcium concentration which increases the aerobic and anaerobic metabolism.
As a result, this causes an increased body temperature, acidosis and muscle rigidity leading to death
How is malignant hyperthermia treated
Dantrolene - a RYR channel blocker
What are the different features of IP3 and ryanodine when considering skeletal muscle
IP3 - minor
Ryanodine - major
What are the different features of IP3 and ryanodine when considering smooth muscle
IP3 - dominant
Ryanodine - minor
What are the different features of IP3 and ryanodine when considering caffiene
IP3 - no action
Ryanodine - opener
What are the different features of IP3 and ryanodine when considering ruthenium red
IP3 - no action
Ryanodine - blocker
What are the different features of IP3 and ryanodine when considering heparin
IP3 - inhibitor
Ryanodine - no action
What are the different features of IP3 and ryanodine when considering dantrolene
IP3 - no action
Ryanodine - blocker
What is the role of cyclic ADP-ribose (cADPR)
Finds and binds to ryanodine receptors on the endoplasmic reticulum for calcium release