Electrical and Molecular Mechanisms of the Heart and Vasculature

Question 1

describe the k+ concentration in a normal cell? and how they move? what does this contribute to and why?

Answer 1

• higher intra (145mmol/L) than outer 3.5-5.5mmol/L
• move down their conc gradients
• they set up the membrane potential because membrane higher selective permeability to k+ than other ions

Question 2

describe this graph

Answer 2

4 = resting membrane potential at around -90mv due to membrane being selectively permeable to k+ so they leak out cause negative intracellular charge

0 = stimulus causes the sodium channels to open DEPOLARISATION.

1 = na+ inactivate and k+ channels open, there a rapid efflux of k+ outside the cell causing the straight dip known as TRANSIENT OUTWARD K GRADIENT.

2= with k+ efflux, L-type Ca2+ channel open and calcium enters the cells, and due to the equal amounts of pca2+ entering and K+ leaving we reach PLATAUE PHASE.

3= due to greater k+ efflux ca2+ channels close and K+ efflux results in the continued repolarisation until resting membrane potential is reached of around -90mv

Question 3

when looking at ECG what are we looking at and why?

Answer 3

DEPOLARISATION AND REPOLARISATION moving through the heart

depolarisation , because it preceeds contraction,so any issue with depolarisation = issue with contraction

• also between depolarisaton cycles you can determine how well repolarisation is occuring because you must undergo repolarisation before depolarsationcan occur

Question 4

how do all myocytes get depolarised from those close to SAN

Answer 4

• na+ move into neighbouring myocytes via gap junctions and cause the their mp to increase (more positive ) until threshold value is reached and AP is fired. this is known as propogation of the action potential

Question 5

describe the SAN AP

Answer 5

• pacemaker potential at the start due to HYPERPOLARISATION-ACTIVATED,CYCLIC,NUCLEOTIDE,GATED CHANNEL = which allows the movement of sodium into the cell, so closer to threshold value.
• threshold reached and AP fired, DEPOLARISATION
• REPOLARISATION
• the K+ channels are slow to close and so we go into hyperpolarisation. the more we hyperpolisation the more we activate the HCN channels and so more influx of sodium into the cell

Question 6

what happens if SAN doesnt function

Answer 6

use AVN but slower AP rhythm

Question 7

why is SAN important

Answer 7

establishes the heart rhythm = natural automacity

Question 8

what contriibutes to messed up heart rhythm

Answer 8

hyper and hypokalaemia

Question 9

hyperkalaemia

Answer 9

• more than 5.5mmol/L k+ in blood [ 5.5-5.9 mild /6.0-6.4 moderate/6.5<severe></severe>
• causes ; decreased dietary intake, excess excretion (laxatives, diuretics,Na-K+ pump issue herediaty)
• results in less k+ leaving cell since membrane selectivility permeable to k+ so more positive membrane potential so more likely to reach thresholdc TACHYCARDIA initially, but prolonged activationof sodium channels causes then to inactivate and so ASYSTOLE resulting in CARDIAC ARREST
• treatments ; calcium gluconate = they cause the membrane potential to be more negtaive and restore it / insulin = b casues K+ to enter cells because it stimulated the NHX to c NA+ entry into cell and so the NAK+ pump is in turn activated to pump that sodium out, in turn causing K+ into cells / glucose is given due to the insulin

Question 10

hypokalaemia

Answer 10

• less than 3.5mmol/L of k+ in the blood
• membrane potential is more negative and so less likely for AP = BRACHYCARDIA since lengthens the AP nad also delays repolarisation because it inhibits the k+ channels , this makes it more likely that the heart will experience arrhthymia ,ie VENTRICULAR FIBRILLATION ( this beause longer AP can result in early after depolarisations (EADs) which cause oscillations in the membrane potential and result in VF

Question 11

describe the excitation-contraction coupling of the vascular system

Answer 11

• Ca2+ travel down T-tubules and cause opening of VGCC which allow calcium into cell
• also noradrenaline bind to alpha1 inhibitory receptors and activate the gi causing DAG and IP3 to dissociate, IP3 binds to SERCA and increase in the intracellular ca2+
• 4ca2+ binds to calmodulin and this binds ot MLCK and activates it , where by it adds a pi group ot myosin head to activate it and allow for contraction
• MLCP which constituently active (always active in the background) is present but the DAG activates PKC whch inhibits it allowing the MLCK to continue to keep myosin head in active form
• MLCP then finally removes the pi from myosin head to inactive it when ca2+ stop as a result of the stop na+

Question 12

excitation-coupling of the mycoytes

Answer 12

• depolarisation occurs….k+ efflux, ca2+ influx
• so….. ca2+ ions pass down T-tubules upon depolarisation. ( influx due to opening of th L-type ca2+ channels)
• increase intracellularly activates ryanodine-receptor-channel which allow for ca2+ movement from SERCA,
• ca2+ binds to troponin ….
• 25% sarcolemma 75% stores