Excitation-Contraction Coupling Flashcards
What is each myofibril surrounded by
Sarcoplasmic reticulum
What is a t-tubule, what does it do
T-tubules are invaginations of the sarcolemma that penetrate the fibre at junctions between the A/I bands in each half sarcomere
What is contained in the T-tubules
ECF- extra cellular fluid
What is part of the endomembrane system
SR
What does t-tubule stand for
Transverse tubule
What is contained in a triad
Two SRs about a T-tubule
SR cisterna/ t-tubule/ SR cisterna
What is the terminal cisternae and what is its importance
Region of SR nearest to the t-tubule (bulged end)
This is where excitation-contraction coupling begins
What causes the AP in postsynaptic cell
Opening of NAChR results in passive EPP where Nav channels open causing AP
Where are DHPR found and what is there actual name
L-type Ca channel
Localized to t-tubules
Where are RYR found and what are they coupled to
Localized to SR membrane
Mechanically coupled to DHPR
Where is Ca released from specifically
Terminal cisterna of SR
What is calsequestrin and where is it found
Is a calcium binding protein- reduces SERCA activity by decreasing Ca gradient
Low affinity for Ca- let’s go easily, needs high Ca to work
Found in SR- close proximity to RYR
What type of channel is DHPR
Cav1.1 (L-type)
What type of RYR channel
RYR1
What can summation of twitches produce
Unfused or fused tetanus
What is a twitch
Contraction and relaxation of muscle
Explain time scale of events neuronal AP to muscle twitch
Neuronal AP- muscle AP- increase intracellular Ca and twitch starts- decreased Ca and twitch ends
After end plate potential depolarizes to threshold explain the steps until Ca re-uptake after contraction
- Voltage gated Na channels open
- muscle AP spreads over sarcolemma and into T-tubules
- Muscle AP depolarization opens DHPR (L-type Ca channels)
- Mechanically coupled DHPR and RYR1 causes RYR1 to open and Ca release from SR
- Ca bind to TnC, after contraction Ca pumped back into SR by SERCA
Explain physical set up on DHPR and RYR
4 Cav1.1 channels for 1 RYR
Every other RYR interacted with
How are Cav1.1 and RYR1 physically coupled
Protein-protein interactions
Voltage induced conformational change in DHPR is transduced to RYR
What are benefits to physical coupled DHPR and RYR vs Ca-induced Ca release
- Faster, more efficient- accelerate E-C coupling
- Don’t have to pump Ca back out of cell (NCX)- this reduces ATP consumption
How are Cav1.1 channels grouped
Tetrads (4)
Seen in freeze fractures
What is the “foot” a part of and where is it located
Each RYR1 has a foot that extends into cytosol
Name specific thing that couples DHPR and RYR1
Specific amino acid residues in II-III linker
Linker interact with RYR1 foot
What is Cav1.1 impact on contractility, what study proved this
No impact
Creates inward Ca current but when pore was blocked in mice contraction still fine due to physical coupling
What are some Cav1.1 inhibitors and what are they used for
Dihyropyradine blocks channels
(ex. Nifedipine- antihypertensive for blood vessels)- DHP related
(ex. Verapamil- anti arrhythmogenic for cardiac) -not DHP related
Used to manage angina (chest pain), cardiac arrhythmia, high blood pressure, anti-hypertension
SERCA function
Pump Ca against large concentration gradient
High density of pumps on SR membrane
Is the cost of muscle contraction high or low
High metabolic cost
Calsequestrin location and capacity
Within terminal cisternae- highly localized beneath triad junction
Has high capacity for Ca binding but low affinity
How does calsequestrin aid in E-C coupling
Unloads Ca near RYR1 therefore allowing for SR Ca release
Where does Ca bind for muscle contraction and how many
4 Ca bind to TnC- causes conformation change in TnI
2 high affinity binding sites that bind Mg2+ at rest
2 low affinity bind as Ca concentration rises
Also EF hands available- when Ca very low or very high
What is moved to expose myosin binding site on actin
Tropomyosin
Function TnT, TnI, TnC
TnT- binds tropomyosin
TnI- binds actin
TnC- binds Ca
Force vs Ca concentration graph shape and 50%
Sigmoidal shape
Start 0.1 microM
50% max force at 1microM
Contractile force is Ca dependent
