Flashcards in Cellular and Molecular Events in the CVS Deck (79):
Does Na/K-ATPase set the RMP?
What happens to RMP if the sodium pump is blocked?
It only changes by 5-7mV
What is the RMP set by?
Due to K permeability of the cell membrane at rest
What state are K channels in at rest?
What channels do cardiac myocytes possess?
Inward rectifier K channels
How permeable to other ions are cardiac myocytes?
Only a small permeability
What can be said of cardiac myocytes?
They are electrically active
What is meant by cardiac myocytes being electrically active?
They fire action potentials
What do action potentials trigger?
An increase in cytosolic [Ca]
What is a rise in calcium required for?
To allow actin and myosin interaction
What does actin and myosin interaction generate?
How do action potentials in heart cells differ from those in nerves and skeletal muscle?
They are much longer
What are the stages in the ventricular (cardiac) action potential?
Opening of voltage gated Na channels causes a rapid depolarisation, from RMP to +30mV as Na enters the cell
Transient outward K current causes a return towards a lower membrane potential, reaching +10mV
Membrane potential lowers to about -10mV because of opening of voltage gated Ca channels
Ca channels inactivate and voltage gated K channels open, causing return to RMP
What is rapid depolarisation due to opening of Na channels called?
What might happen after the initial depolarisation that contributes to a lower membrane potential?
Might get some reversal of Na/Ca transport
What may also happen when the voltage gated Ca channels are open?
May be some K channels open, allowing efflux of K
What do cardiac myocytes possess lots of different types of?
Draw the ventricular action potential
Why do cardiac myocytes have lots of different types of K channels?
Because they each behave in a different way, and contribute differently to the electrical properties of the cell
What is the SA nodes set membrane potential?
Doesn’t really have one
Why does the SA node not really have a set membrane potential?
Because the whole time, there is a long, slow depolarisation
What is the SA nodes long, slow depolarisation called?
The pacemaker potential
What causes the pacemaker potential?
Influx of Na
What happens as Na channels open?
Na ions go in to cause a little bit of depolarisation, but become inactivated in accommodation due to long depolarisation
What is the result of the Na channels becoming inactivated by the long depolarisation?
The upstroke cannot rely on Na channels, it also needs voltage gated Ca channels
What is the initial slope to threshold of the SA node action potential known as?
The funny current
When is the SA node action potential activated?
When it reaches membrane potentials that are more negative than -50mV
What is the result on the SA node action potential when the membrane potential reaches a more negative level?
The more it activates
What channels does the funny current use?
How are HCN channels activated?
How are HCN channels controlled?
What do HCN channels allow?
Influx of Na ions, which depolarises the cell
Describe the process of the SA node action potential
Voltage gated Ca channels when the membrane potential reaches -50mV, causing depolarisation
Opening of voltage gated K channels cause repolarisation
What does the opening of voltage gated Ca channels cause in the SA node action potential?
What does the opening of voltage gated K channels cause in the SA node action potential?
How does the SA node action potential differ from the ventricular?
It is not as quick
Why is the SA node action potential not as quick as the ventricular?
Because calcium channels open more slowly
What is the SA node action potential said to have?
What is said of the membrane potential of the SA node?
It is unstable
Does the action potential waveform stay the same throughout the heart?
No, it varies
What part of the heart is fastest to depolarise?
What is the result of the SA node being the fastest to depolarise?
It sets the rhythm
What other parts of the conduction system have automaticity?
Why doesn’t the AV node set the rhythm?
It depolarises slower
What path does the cardiac action potential take?
Travels from SA node, to AV node, down bundle of His to bundle branches
What are the bundle branches in the heart?
Left (posterior division)
Left (anterior division)
What are the features of cardiac muscle?
Single central nuclei
How are cardiac muscle cells joined?
Structurally by desmosomes
Electrically by gap junctions
What do desmosomes do?
Rivet cells together
What do gap junctions do?
Allow for rapid transfer of ions
What does depolarisation that happens during the ventricular action potential do?
Opens L-type Ca channels in the T-tubule system
Where is the T-tubule system localised?
Close to the SR
What does localised Ca entry due to channels opening cause?
Opening of calcium-induced calcium release (CICR) channels in the sarcoplasmic reticulum
What is closely linked to L-type channels?
Ca release channels
What % of calcium enters across the sacrolemma, through L type channels?
What % of calcium is released from the SR?
How is cardiac myocyte contraction regulated?
Ca binds to troponin C, and a conformational change shifts tropomyosin to reveal myosin binding site on actin filament
What must happen to relax cardiac myocytes?
Must return intracellular [Ca] to normal levels
How is intracellular [Ca] returned to normal levels?
Most pumped back into SR
Some exits across plasma membrane
How is Ca pumped back into the SR?
What stimulates the SERCA pumps?
How does Ca exit across the cell membrane?
What is tone of blood vessels controlled by?
Contraction and relaxation of vascular smooth muscle cells
Where are the vascular smooth muscle cells located?
In the tunica media
What is present in the tunica media?
Multiple circularly arranged smooth muscle layers
What vessels have vascular smooth muscle cells?
Arteries, arterioles and veins
How is vascular smooth muscle different from striated muscle?
Don’t have the same arrangement of actin and myosin
How are actin and myosin arranged in vascular smooth muscle?
Connected to dense bodies, and radiate out
At what level does regulation of cardiac contraction occur?
Of the myosin head
How does the myosin head regulate cardiac contraction?
It has a regulatory light chain
What happens when light chain on the myosin head is not phosphorylated?
It can’t bind to actin
How is myosin activated?
Myosin light chain kinase (MLCK) phoshorylates myosin
Why does MLCK need to be controlled itself?
To prevent it from activating myosin all the time, and contraction happening all the time
How is MLCK controlled?
How does calmodulin activate MLCK
Calmodulin can bind 4 calcium ions. Calcium can either
come from voltage gated calcium channels, or from SR.
In smooth muscle cells, there are adrenoreceptors- α-1
receptors. If noradrenaline binds these receptors, it causes production of IP 3
which then causes release of calcium from SR. Calcium binds to
calmodulin, which activates MLCK.
How is MLCK activation terminated?
Myosin light chain phosphatases
When are MLCPs active?
Constitutively- active all the time
How are MLCPs regulated?
When noradrenaline binds to alpha-1 receptor, also
forms DAG, which activates protein kinase C- phosphorylates MLCP, inhibiting