Lecture 9- Electrical and molecular mechanisms in the hearts Flashcards
which ion set shte resting membrane potential
K+ permeability
- high conc of K+ intracellularly
- lower conc of Na+ intracellularly
At rest the cardiomyocyte are permeable to
K+ ions
at rest K+ ions move out of the cell
down conc gradient
what makes the inside negative with respect to the outside at rest
small movement of ions
- as charge builds up an electrical gradient established–> K+ moves back in
When chemical and electrical gradients are equal but opposite- no movement
- RMP
Net outflow of K+ until Ek reached
why is resting potential not equal to Ek
small permeability to other ion species at rest
Excitation contraction coupling
- Cardiac myocytes are electrically active- fire AP
- AP triggers release of calcium into cytosol
- A rise in calcium is required to allow actin and myosin interaction
- Generate tension-contraction
Different types of APs in different tissues - have different features such as
Different lengths
Cardiac myocyte lasts 280ms (much longer than axonal or skeletal)
4 types of AP
axonal
skeletal muscle
SAN
Cardiac ventricle
APs are measured using
microelectrode
How is the equilibrium potential of potassium (resting potential) set up?
Chemical diffusion and electrical gradients
1) Chemical diffusion: Potassium flows out of the cell down its concentration gradient via diffusion
2) Electrical gradient: causes potassium to flow back in due to the negativity created by K+ initially leaving the cell down its conc gradient (and also intracellular anions)
When these forces are equal and opposite- no net movement of potassium - negative membrane potential due to anions
resting membrane potential of axon
-70mV
resting membrane potential of skeletal muscle
-90
resting membrane potential of SAN
-60mV
resting membrane potential of cardiac ventricle
-90mV
what is membrane potential
Membrane potential is the electrical charge that exists across a membrane
draw and label the ventricular (cardiac) AP
Ek of the cardiac AP
-90-95mV
ENa of Cardiac AP
+70 mV
phases of the cardiac AP
- RMP due to background K+ channels (not V-gated)
- Upstroke due to opening of voltage-gated sodium channels- Na+ influx
- Initial repolarisation due to transient outward K+ channel (V-gated)
- Plateau due to opening of voltage gated Ca2+ channels (L-type)- influx of calcium
- Balanced with K+ efflux
- Inactivation of calcium channels. Repolarisation due to efflux of K+ through voltage gated K+ channels and other
which type of voltage gates calcium channesl
L type
draw and label the SAN AP
the SAN is knwon as the
pacemaker- where the electrical activity originates
outline the SA node action potential
- Long slow depolarisation to threshold (starting at -60mV)- due to funny current
- Upstroke- Opening of V-gated calcium channels
- V-gated Sodium channels not involved (would make them all inactive)
- Downstroke- Opening of V-gates K+ channels
Funny current- If
HCN channels
- Hyperpolarisation-activated cyclic nucleotide-gated channels (responsible for spontaenous depolarisation)
- Allow influx of Na+ ions which depolarises the cells
- Upstroke
SAN AP is similar to
AV AP
IF SAN not working the
AVN would take over as the pacemaker (just slower than the SAN)
Aps throughout the heart
- SA and AVN both have unstable resting membrane potential
- Atrial muscle fibres-like ventricular muscle
- Purkunjee- in-betweens SA and ventricular muscle AP
- Slight If (funny current- incline at the beginning)
Purkunjee fibres
- in-betweens SA and ventricular muscle AP
Slight If (funny current- incline at the beginning)
If AP fires too slowly
- bradycardia
If AP potential fail
asystole
is the most serious form of cardiac arrest and is usually irreversible. A cardiac flatline is the state of total cessation of electrical activity from the heart, which means no tissue contraction from the heart muscle and therefore no blood flow to the rest of the body.
If AP fire too quickly
tachycardia
If electrical activity become random
–> fibrillation
Plasma [K+] must be controlled within tight range
– 3.5-5.5 mmol/l-1
hyperkalaemia
>5.5 mmol L-1
Hypokalaemia
<3.5 mmol L-1
Why are cardiac myocytes so sensitive to changes in [K+]?
K+ permeability dominates RMP
The heart has many different kinds of K+ channels –> some behave in peculiar ways
hyperkalaemia effect on the heart
Hyperkalaemia depolarises the myocytes and slows down the upstroke of the action potential
why does hyperkalaemia depolarises the myocytes and slows down the upstroke of the action potential
- EK = 61.5mV Log [K+]o / [K+]i
- If you raise plasma K+ then EK gets less negative so the membrane potential depolarises a bit
- This inactivates some of the voltage-gated Na+ channels
- Slows upstroke
*dotted line= hyperkalaemia*
risk of hyperkalaemia
- Heart can stop- asystole
- May initially get an increase in excitability
- Depends on the extent and how quickly it develops
- Mild 5.5-5.9 mmol/L
- Moderate 6-6.3 mmol/l
- Severe >6.5mmol/l
treatment of hyperkalaemia
- Calcium gluconate
- Calcium makes the membrane less excitable
- Insulin and glucose
- Wont work if hearts already stopped
hypokalaemia and cardiac AP
- Lengthens the action potential
- Delays repolarisation
More brown line =effect of hypokalaemia
hypokalaemia can lead to
early after depolarisation (EAD)–> this can lead to oscillations in mem potential–> Can result in ventricular fibrillation
outline Excitation contraction coupling in the heart
- Depolarisation opens L-type calcium channels in T-tubule system
- Localised entry of calcium (25% of total calcium influx into cytosol) opens Calcium induced calcium release (CICR) channels in the SR (75%)
- Close link between L-type channels and Ca2+ release channels
Regulation of cardiac myocyte contraction
- Calcium binds to troponin C
- Conformational change shifts tropomyosin to reveal myosin binding site on actin filament
Relaxation of cardiac myocytes
- Must return (Ca+2) to resting levels
- Most is pumped back into SR (via SERCA)
- Raised calcium stimulates the pump
- Some exit across cell membrane
- Sarcolemmal Ca2+ ATPase
- Na+/Ca2+ exchanger
Tone of blood vessel is controlled by contraction and relaxation of vascular smooth muscle cells
- Located in tunica media
- Present in arteries, arterioles and veins
E-C coupling in smooth muscle
- Opening of VOCC or activation of GalphaQ ( Alpha 1 receptors)
- Calcium influx from extracellular space or SR
- Calcium binds to Calmodulin (x4 calcium ions)
- Activated calmodulin activates to Myosin light chain kinase (MLCK)
- MLCK now phosphorylates the myosin light chain
- If phosphate isn’t bound- wont bind to actin
- When activated (with phosphate) myosin light chain can bind to actin
- Myosin light chain phosphatase removes phosphate form myosin which allows relaxation
- DAG – produced via GalphaQ will activates PKC- PKC has inhibitory effect on MLCP- keeps Myosin light chain in active form
Myosin light chain must be ………… to enable actin-myosin interaction
phosphorylated
Relaxation of smooth muscle as….
- Calcium levels decline
- Myosin light chain phosphatase dephosphorylates the myosin light chain
Phosphorylation of MLCK by
PKA inhibits the action of MLCK
Inhibits phosphorylation of the myosin chain and inhibits contraction
Difference between cardiac muscle and smooth muscle
Contraction of heart initiated by spread of AP from SA node
No neural input needed
Cardiac myocyte action potential allow calcium entry
- Further calcium released from SR
- Calcium binding to troponin C
Contraction of vascular smooth muscle cells initiated by depolarisation or activation of alpha-adrenoreceptors
- Increased intracellular calcium
- Calcium binding to calmodulin
- Activation of MLK- phosphorylates myosin light chain
