Flashcards in CVS - cellular molecular events Deck (24):
What sets up the resting membrane potential?
Largely set by the K+ permeability of the cell membrane at rest - determined by how many K+ leak channels are open. There's only small permeability to other ions and the sodium pump DOES NOT set the RMP!
What is the role of the sodium pump?
It establishes the sodium and potassium gradients but does not set the RMP.
How does K+ permeability set the RMP?
K+ ions move out of the cell down their concentration gradient. This small movement of ions makes the inside more negative with respect to the outside. As charge build up an electrical gradient is established.
Why is the RMP not the equilibrium potential of K+ (Ek)?
Due to the membrane's small permeability to other ions at rest. The exact value of the RMP differs between cells due to their differing permeability to these other ions.
What causes the upstroke in the AP of a ventricular myocyte?
Opening of voltage-gated Na+ channels
What causes the prolonged AP in ventricular myocytes?
After the upstroke there is a short dip as K+ channels open and then quickly become deactivated. This current is known as I(to). Then voltage-gated Ca2+ channels open (some K+ channels open(I(kv)) and the Ca2+ influx causes a plateau which prolongs the action potential.
Describe the different potassium channels that are involved in the AP of a ventricular myocyte.
1. Potassium leak channels maintain the RMP
2. One type causes the I(to) current which causes transient efflux of K+ after the upstroke
3. Another channel creates the I(kv) current which is active during Ca2+ influx
4.Potassium channels that mediate the I(kv) current and I(kr) current then repolarise the cell back to the RMP
What is the pacemaker potential?
It is the funny current (If) seen in SA node cells - the initial slope to threshold. It is activated at membrane potentials more negative than -50mV (the more negative then more it activates). This current occurs through HCN channels (hyperpolarisation-activated cyclic nucleotide-gated channels). This allows an influx of Na+ ions which depolarise the cell BUT It is NOT an AP.
The SA node has natural automaticity. What is meant by natural automaticity?
It means they do not need any nervous activity or signals from other cells to cause an AP. They are naturally unstable.
What causes the upstroke and downstroke in the SA node action potential?
Upstroke - opening of voltage-gated Ca2+ channels
Downstroke - opening of voltage-gated K+ channels
In what order would other parts of the conducting system take over if the SA node was damaged?
1. AV node
2. Purkinje fibres
What structures in the intercalated disc help to bind cardiac myocytes together and which help them connect electrically?
1. Structural - desmosomes (intercellular junctions)
2. Electrical - gap junctions
What channels of the cardiac myococytes are opened in the T-tubule and sarcolemma in response to an depolarisation?
L-type Ca2+ voltage-gated channels
Entry of Ca2 into cardiac myocytes triggers release of Ca2+ from their stores in the SER by which channel?
Through calcium-induced calcium release channels (CICR)
How much of the Ca2+ influx into the cytoplasm of a cardiac myocyte comes from the SER and how much from the ECF?
How does Ca2+ cause contraction of cardiac myocytes?
By binding to troponin C, causing a conformational change in tropomyosin to reveal the myosin head binding site on the actin molecule and therefore triggering the reverse sliding filament mechanism of contraction.
How is intracellular Ca2+ returned to resting levels during diastole?
75% through SERCA into the SER
25% through sarcolemma Ca2+ ATPase and Na+/Ca2+ exchanger
How is the tone of blood vessel controlled?
By the contraction and relaxation of vascular smooth muscle cells in the tunica media of arteries, arterioles and veins.
How are actin and myosin filaments arranged in smooth muscle?
They are attached to dense bodies in a spiral-like arrangement around the cell.
Describe two pathways that increase the [Ca2+]i in smooth muscle
1. Depolarisation causing opening of V-gated Ca2+ channels
2. NA activation of alpha-1 receptors causing IP3 to bind to Ca2+ channels in the SER membrane and trigger release of Ca2+ from the SER
The myosin-actin interaction in smooth muscle is not mediated by Ca2+ binding to troponin C, what mediates it?
Phosphorylation of myosin's regulatory light chain allows binding to actin. Phosphorylation is by myosin light chain kinase (MLCK).
How does an increase in intracellular Ca2+ result in the activation of MLCK?
Ca2+ binds to calmodulin (a calcium binding protein) which goes on to activate MLCK.
NA acitvation of alpha-1 receptors increases intracellular Ca2+ by triggering its release from the SER. What other affect does the receptor's activation have?
Activation of the alpha-1 receptors activates phosholipase C which creates two molecules by phospholipid cleavage: DAG and IP3. DAG acts as a second messenger and activates PKC. PKC inhibits the constitutively active myosin light chain phosphatase (MLCP). Therefore activation of alpha-1 receptors inhibits inactivation of the myosin heads and therefore helps myosin-actin interactions to occur.