Lecture 3: Cardiac muscle physiology 1 Flashcards
What is the main type of metabolism in myocytes?
Mainly oxidative metabolism
In the myocardium what is the main cell types?
Cardiac fibroblasts (Majority) Myocytes (30%) - Majority of mass Endothelial cells Vascular smooth muscle cells Neurons
Describe the appearance of myocardium longitudinal section;
Striated EC space collagen filled Intercalated discs at intracellular junctions, consists of; - Nexus / gap junctions - Fascia adherins - Macula adherens (desmosomes)
Brief overview of myocyte structure
Sarcolemma: Continuous with T-tubules, contains ion channels
T-tubules at Z disc, Rich in L-type Ca channels (DHPR)
Sarcolemma-SR junctions (Lego hand shape, SR doesnt wrap entirely around), RyR
SR- RyR, SERCA, Calsequestrin, Phospholambam
What is EC coupling?
Excitation-contraction coupling
Describe EC coupling stages;
- Activation of Ica (L type Ca channels)
- Ca induced Ca release (SR RyR)
- Force development
Describe what changes L-type Ca channel function
- Stimulated by catecholamines
- Inhibited by Ca channel blockers and Mg
- Inhibited by low plasma Ca and vice versa
Write some notes on SR;
Reservoir of Ca
- Ca buffered in SR by calsequestrin
- 35-40Ca ions per calsequestrin
SR Membrane contains;
- RyR channels at junctional SR
- SR Ca ATPase (SERCA) regulated by phospholambam
What happens when SR Ca is high?
- Increased Ca available for release
- Enhanced gain of EC coupling (fraction of Ca release for any given ICa trigger)
What regulates RYR2?
Many things including Ca
Describe Ca cycling;
SERCA -> Uptakes plasma Ca and NCX
CICR trigger
RYR2 opens and Ca release
High plasma Ca closes RYR2
Describe EC coupling;
- AP from adjacent cell spreads across SL.
- Depolarisation opens L-type Ca channels (DHPRs)
- Ca influx opens RYR causing SR Ca release
- Ca ions bind to TnC and initiate crossbridge cycling
= Contraction
Describe myocyte relaxation;
- Occurs when [Ca]i is reduced, and Ca unbinds from TnC
- Bulk of Ca is pumped back into SR for storage, NCX takes Ca out of cell
- [Na]i gradient maintained by Na/K ATPase
What are the four important Ca exchangers in myocyte relaxation?
- SERCA
- Ca ATPase (out of cell)
- NCX (out of cell)
- Mitochondrial Ca uniporter (into mitochondria)
In steady state what is the flow of Ca?
- Steady state Ca influx = efflux
What must occur in order for relaxation?
Intracellular Ca must be restored to resting (diastolic) levels
How is Ca restored?
- Muscunaric (Ach) driven CaATPase at the sarcolemmal membrane
- NCX (Forward mode) - This removes Ca that mainly entered via L-type Ca channels. (Reverse mode during early AP can contribute to Ca influx)
- SERCA and Ca mitochondrial uniporter
Describe myocyte relaxation: (specific wording)
- Occurs when iCa is reduced, and Ca unbinds from TnC
- BULK of Ca is pumped back in SR for storage and SMALL amount leaves cell via NCX
- iNa gradient maintained by Na/K ATPase
What happens if Ca efflux is decreased? or Ca influx is increased?
- If Ca efflux is decreased
1) Higher SR Ca
2) increased Ca efflux to balance the influx.
If Ca influx increases these will both occur also
Ca regulates extrusion to always try maintain Ca balance
Do we care about the SL Ca ATPase?
Not really as no drugs target it and its very slow, minor contributor to Ca extrusion
Describe the contribution of NCX to Ca extrusion: and what stimulates its activity.
Ca extrusion (Forward mode) depends on electrochemical gradient.
- Stimulated by low iNa, high Ca and -ve membrane potential
Describe the contribution of NCX to Ca influx: and what stimulates it
Ca influx depends on electrochemical gradient
- Stimulated by high iNa, low iCa, and more +ve membrane potential.
Describe the Ca cycle across the SL during depolarisation:
- DHPRs contribute to most of Ca plateau
- NCX contributes to maintained Ca plateau and then switches to forward mode during early repolarisation
