Cellular And Molecular Events Flashcards
How is the RMP of cardiac Myocytes generated in 4 steps
1- Myocytes are permeable to K+ at rest
2- K+ diffuse out of cell
3- Small movement of ions makes inside -ve relative to outsie
4- Electrical gradient established as charge build up
Describe the 4 stages of the Ventricular Cardiac Action Potential
- Depolarisation- Voltage gated Na+ channels open
- Initial Repolarisation- K+ leave through voltage gated channels
- Plateau- Ca influx balanced roughly by K efflux
- Proper Repolarisation- K efflux, Ca channels inactivate
Describe the 3 stages of the SA Node Action Potential
- Pacemaker Potential, If: Opening of slow Na channels, depolarisation towards threshold
- Upstroke: Ca influx through voltage gated channels
- Downstroke/ repolarisation: K efflux
What channels control the Pacemaker potential?
When are they activated, how are they related to RMP
- HCN (Hyperpolarization-activated, Cyclic Nucleotide-gated channels)
- Activate at membrane potentials below -50mV
- More (-)ve= More activation
State the 4 possible outcomes when Action Potentials don’t fire correctly
- APs fire too slow- Bradycardia
- APs fire too fast- Tachycardia
- APs fail- Asystole
- APs fire randomly- Fibrillation
What is the normal Plasma K+ Range
State the ranges for Hypo and Kyperkalemia
3.5-5.5 mmol/L
Hyperkalemia: >5.5 mmol/L
Hypokalemia: <3.5 mmol/L
Explain the effects of Hyperkalemia in 4 steps
- Ek becomes less negative
- Membrane potential becomes less negative and depolarises
- This causes upstroke to slow down as some of the Na channels inactivate
- Thus slow depolarisation
What are the risks of Hyperkalemia
What are the ranges of Mild, Moderate, Severe Hyperkalemia
How does increased severity affect Na channels and depolarisation
- Asystole
- May get Initial excitability which -> Ceased conductance
Mild: 5.5-5.9 mmol/L
Moderate: 6-6.4 mmol/L
Severe: >6.5 mmol/L
As severity increases, more Na channels inactivate and depolarisation gets slower
What are 2 treatments for Hyperkalemia
Why do they work
When don’t they work
Calcium gluconate (Ca shields membrane)
Insulin + glucose (Insulin drives K into cell, Glucose to counter insulin)
Don’t work if heart already stopped
Explain the effects of Hypokalemia in 4 steps
- Ek becomes more negative
- Membrane potential is more negative
- Longer plateau phase-> Longer Action Potential
- Repolarisation is slower
Outline 2 problems with Hypokalemia
- Longer APs lead to Early After Depolarisations (EADs)
- Leads to membrane potential oscillations-> Ventricular Fibrillations
Explain Excitation-Contraction Coupling in Myocytes
How much Ca is from SR, how much from plasma
- Depolarisation opens L-type Ca channels in T-tubule system
- Localised Ca entry opens closely linked CICR channels in SR
75% from SR, 25% from plasma
Explain relaxation of cardiac myoctes in 3 steps
- Intracellular [Ca] must return to resting level
- High [Ca]i stimulates Ca to be pumped into SR
- Some Ca leaves through PMCA and NCX on sarcolemma
What controls blood vessel tone?
Where are these structures found
Contraction and relaxation of Vascular Smooth Muscle Cells in Tunic Media
Explain Excitation-Contraction coupling in Smooth Muscle in 4 steps
- Ca (From SR and Plasma) binds to Calmodulin
- Ca-Calmodulin binds to and activates MLCK (Myosin Light Chain Kinase)
- MLCK phosphorylates and activates the Myosin Light Chain, so it can interact with actin
- Contraction mechanism begins
