Cardio Flashcards

1
Q

What is the function of the heart?

A

Forces blood around the body

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2
Q

What is the function of the arterial system?

A

Distributes the blood and acts as a pressure reservoir

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3
Q

What is the function of the capillaries?

A

Transfer metabolites between blood and tissue

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4
Q

What is the function of the venous system?

A

Blood storage reservoir and return route

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5
Q

What is the primary function of the cardiovascular system? (3 points)

A

1) Carry metabolites to, and waste products from, the tissues.
2) Communication between tissues by transporting hormones.
3) Involved in heat regulation.

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6
Q

What is the distribution of the heart at rest?

A
60-70% - veins and venules
10-12% - pulmonary circulation
10-12% - systemic arteries
8-11% - heart
4-5% - systemic capillaries
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7
Q

What ensures the output from the left and right compartments of the heart is equal?

A

Frank Starling mechanism (states that the stroke volume of the heart increases in response to an increase in the volume of blood filling the heart when all other factors remain constant)

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8
Q

What is the function of valves?

A

Dictate the direction of flow (stop backflow)

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9
Q

What are the 5 changes in heart shape during the cardiac cycle?

A

1) Ventricular diastole - rapid filling
2) Atrial dystole
3) Ventricular systole - isovolumetric phase
4) Ventricular systole - ejection phase, atrial refill
5) Ventricular diastole - isovolumetric phase

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10
Q

What is stroke volume?

A

Volume of blood leaving the left ventricle during one contraction

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11
Q

What regulates valve opening and closing?

A

Changes in pressure and fluid velocity (a transient reversal of flow causes valves to close)

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12
Q

What is the stroke volume at rest?

A

70ml

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13
Q

What is the resting heart rate?

A

60 beats/min

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14
Q

What is the minimum duration of diastole to ensure adequate ventricular refilling? And what is the maximum heart rate to allow this?

A

0.13s and 180 beats/min

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15
Q

What is the Frank Starling mechanism?

A

The greater the stretch of the ventricle in diastole, the greater the stroke work achieved in systole

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16
Q

What is the cellular basis the the Frank Starling mechanism?

A

Maximum number of cross bridges need to be formed for strongest contraction - if overstretched, unable to form as many cross bridges and so contraction would be less forceful (plus change in calcium sensitivity causes the relationship between force of contraction and sarcomere length to be much steeper than in skeletal muscle)

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17
Q

What prevents overfilling of the heart?

A

Strong parallel elastic component that imparts a stiffness

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18
Q

What is Laplace’s law?

A

For a hollow sphere, the pressure is proportional to the wall tension and inversely proportional to the internal radius (like blowing up a balloon)

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19
Q

How do Laplace’s law and the Frank Starling mechanism work together in a healthy person?

A

They work in opposition but the Frank Starling mechanism is dominant

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20
Q

What is Cv (venouse compliance)? And what does a decrease in Cv cause?

A

Measure of how distensible the veins are. Decrease in Cv means that less blood is stored in the veins

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21
Q

What does Guyton’s cross plot show?

A

As central venous pressure increases, flow also increases and where the two line cross gives cardiac output. Sympathetic stimulation causes increased flow and decreased central venous pressure and therefore cardiac output is increased

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22
Q

How is the amount of blood that reaches an organ controlled?

A

Smooth muscle control the diameter of the arterioles and therfore how much blood enters an organ

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23
Q

Describe conduit (muscular arteries)

A

Arteries that can contract and have a thick wall preventing pinching

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24
Q

Describe resistance vessels and their function

A

Vessels with a lot of smooth muscle in tight regulation with the ANS and metabolites - these are mainly responsible for regulation of blood pressure

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25
Q

What are the two structural differences between arteries and veins?

A

Arteries have serosa (thicker smooth muscle and connective tissue) and veins have valves

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26
Q

What are two roles of the endothelium lining blood vessesl?

A

1) Regulation of blood vessel diameter

2) Control of blood clotting

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27
Q

What is the function of smooth muscle in blood vessels?

A

Contractile and produces the active component of tension in a vessel wall

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28
Q

What is the function of elastin in blood vessels?

A

Enables expansion during systole

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29
Q

What is the function of collagen in blood vessels?

A

Limits vessel expansion under pressure

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30
Q

What is different about blood flow in capillaries?

A

No pulse, constant slow flow of blood allowing metabolite exchange to occur

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31
Q

What purpose does the expansion of large arteries during systole serve?

A

The compliance (ability to stretch) of the larger arteries acts as a hydrolic filter, converting pulsatile flow generated by the heart to a steady flow through capillaries

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32
Q

What is the equation for flow?

A

Q = (P1-P2)/R (Q = flow, P = pressure, R = resistance)

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33
Q

How does a hydraulic resistance in series affect R?

A

Rt = R1 + R2 + R3 + … + Rn

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34
Q

How does a hydraulic resistance in parallel affect Q and R?

A
Qt = Q1 + Q2 + ... + Qn
Rt = 1/R1 + 1/R2 + ... + 1/Rn
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35
Q

What is Poiseulle’s law equation for flow and for resistance?

A
Q = (π(P1-P2)r^4)/8nL (Q = flow, P = pressure, r = radius, n = viscosity, L = length)
R = (8nL)/(πr^4) (R = resistance, n = viscosity, L = length, r = radius)
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36
Q

What does Poiseulle’s law state?

A

The velocity of the steady flow of a fluid through a narrow tube varies directly as the pressure and the fourth power of the radius of the tube and inversely as the length of the tube and the coefficient of viscosity (blood cells forced to the middle of the vessel, stops blood from getting stuck, reduces viscosity through small vessels)

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37
Q

What does Bernoulli’s theory state?

A

The total mechanical energy of the flowing fluid, comprising the energy associated with fluid pressure, the gravitational potential energy of elevation, and the kinetic energy of fluid motion, remains constant (at a narrow section of blood vessel, the pressure will decrease as there is a lot of kinetic energy - law of energy conservation)

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38
Q

What are the consequences of Bernoulli’s theorum to the circulation?

A

High blood velocity throught the narrowed part of the artery leads to low intraluminal pressure which exacerbates the narrowing

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39
Q

Bearing Bernoulli’s theorum in mind, what would relieve sympotoms in a person with narrowing of their blood vessels?

A

Increase luminal diameter - this would slow the velocity of the blood and increase intraluminal pressure which would help keep the artery open

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40
Q

How is local circulation controlled?

A

Independently regulating the diameter of arteries supplying blood to that area (vasodilation, vasoconstriction)

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41
Q

What causes heart rate at rest to be slower than the intrinsic rate of the SAN?

A

Maintained sympathetic activity known as vagal tone

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42
Q

What are the baroreceptors stimulated by and what do they cause (6 points)?

A
Stimulated by distension (by increased blood pressure) of the structures in which they are located.
They cause:
1) Increased vagal parasympathetic output
2) Inhibition of sympathetic output
3) Vasodilation
4) Decreased blood pressure
5) Drecreased heart rate
6) Decreased myocardial contractility
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43
Q

What are the chemoreceptors stimulated by and what do they cause (5 points)?

A

Stimulated by a decrease in PO2 and an increase in PCO2 or by reduced blood flow to the carotid and aortic bodies.
They cause:
1) Increased sympathetic vasomotor activity
2) Constriction of peripheral circulation
3) Increased blood pressure
4) Indirect increase in heart rate
5) Alterations to the respiratory system

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44
Q

Give a brief overview of the renin-angiotensin system

A

Renin is stored in the juxtoglomerular kidney cells. An intrarenal baroreceptor mechanism regulates renin release. Renin is released in response to low renal blood pressure, low concentration of sodium-chloride at the macular densa and sympathetic stimulation. Renin converts angiotensin to angiotensin I and angiotensin converting enzyme converts angiotensin I to angiotensin II which is a powerful vasoconstrictor therfore increasing blood pressure

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45
Q

Name two morpholgical difference between cardiac myocytes and smooth muscle myocytes

A

1) Cardiac myocytes have striations

2) Cardiac myocytes are bigger and more rectangle (like building blocks)

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46
Q

Name three differences between cardiac muscle and smooth muscle contraction

A

1) Cardiac muscle contraction is initiated by an action potential whereas smooth muscle contractile tension in related to cytosolic [Ca2+] (smooth muscle is non-excitable - can’t fire action potentials)
2) Cardiac action potential produces contractile twitch whereas changes in membrane potential of smooth muscle causes a more graded response
3) Cardiac muscle: calcium entry during the action potential plateau causes calcium dependent calcium release; smooth muscle: resting membrane potential regulate calcium entry (calcium entry increases with depolarisation.

In both, calcium activates contractile proteins

47
Q

What four types of membrane proteins facilitate transportation of large polar molecules and ions across the lipid bilayer?

A

1) Channels (use electrochemical gradient, rapid) e.g. K+, P2X
2) Carriers/exchangers (use concentration gradient) e.g. GLUT1-4
3) Primary active transport (use ATP as energy source) e.g. Na+/K+ ATPase
4) Secondary active transport (Use ionic gradient as energy source) e.g. Na+/Ca2+ exchanger

48
Q

What are the three types of facilitated diffusion?

A

1) Uniport
2) Symport
3) Antiport

49
Q

What is the equation for Fick’s law of diffusion?

A

J = DA(dc/dx/) (J = flux, D = diffusion coefficient, A = area for diffusion, dc/dx = concentration gradient)

50
Q

How do carrier proteins work?

A

They undergo a conformational change for each transport cycle. Outside gate opens, X enter binding site, both gates close, inside gate opens and X leaves binding site, both gates close and then the cycle starts again (X will only move down its concentration gradient).
(carriers can be saturated - therefore show Michaelis-Menten kinetics)

51
Q

Describe the events that allow active transport of calcium from the cytoplasm into the SR lumen (calcium inside SR is higher than calcium in the cytoplasm). .

A

Two calcium ions bind to SERCA (a calcium ATPase) with high affinity. ATP is hydrolysed to ADP and Pi, ADP leaves and Pi remains bound causing the outside gate to close. The inside gate opens and calcium is released. Two hydrogen molecules bind to SERCA and Pi leaves causing the inside gate to close. ATP binds and causes the outside gate to open and hydrogen is released.

52
Q

What is the Nernst equation and what does it tell us?

A

Eion = (RT/zF)ln([ion]o/[ion]i/) (R = gas constant 8.314JK^-1mol^-1; F = faraday’s constant 96500Cmol^-1; T = Absolute temperature 0 degrees C = 273 K)
It can be used to calculate the equilibrium potential for each ion

53
Q

What is the normal concentration of sodium inside and outside the cell? What is the equilibrium potential? (at -70mV Vm)

A

Inside: 15mM
Outside: 150mM
Equilibrium: 61mV

54
Q

What is the normal concentration of potassium inside and outside the cell? What is the equilibrium potential? (at -70mV Vm)

A

Inside: 150mM
Outside: 5.5mM
Equilibrium: -90mV

55
Q

What is the normal concentration of chloride inside and outside the cell? What is the equilibrium potential? (at -70mV Vm)

A

Inside: 9mM
Outsde: 125mM
Equilibrium: -70mV

Note: concentration much higher in smooth muscle

56
Q

What is the normal concentration of calcium inside and outside the cell? What is the equilibrium? (at -70mV Vm)

A

Inside:

57
Q

What is an equilibrium potential?

A

A balance of diffusional and electrical forces

58
Q

What is the equation for the electrochemical gradient?

A

Vm - Eion (membrane potential - equilibrium potential)

59
Q

How many ions (a lot or little) need to flow to change membrane potential?

A

Very little produce a relatively large change in membrane potential

60
Q

What is a reversal potential?

A

The potential at which no net current flows when channels are open

61
Q

Why might reversal potential of sodium channels be different to the equilibrium potential of sodium?

A

Sodium channel is not perfectly selective for sodium - it allows flow of a small amount of potassium through its pore

62
Q

What is the function of the NCX?

A

Activity of NCX will result in membrane potential attempting to reach the NCX equilibrium potential - this will occur by moving sodium in the appropriate direction

63
Q

What is the equation for the relationship between whole cell and single channel currents?

A

I = NiPopen (I - whole cell current; N = total number of channels; i = single channel current; Popen = open probability)

64
Q

What does voltage clamp meausure?

A

Allows measurement of membrane current at a constant voltage

65
Q

How can the cell currents responding to a voltage pulse be separated and isolated for study? (3 points)

A

1) Ionic substitution
2) Use of voltage protocols
3) Use of specific blockers

66
Q

How do tail currents allow us to study single channel behaviour?

A

As you step the voltage down, there is an immediate change in driving force and this changes the open probability of the channels, but channels will take time to reach the new open probability

67
Q

What does a availability curve show?

A

The proportion of channels not inactivated

68
Q

What is Markov statistics?

A

Single channels open and close in a random manner.
The dwell time in any state will be a random variable and will be distributed exponentially with τ = mean dwell time.
The mean dwell time in any state = 1/(sum of rates for leaving that state)

69
Q

What is the equation for open probability?

A

Popen = to/(td + tc) = β/β + α (to = time open; td = mean open time; tc = time closed) (closed to open = β; open to closed = α)

70
Q

What is the selectivity for sodium channels, potassium channels and calcium channels?

A

Sodium channels - not very selective
Potassium channels - quite selective
Calcium channels - very selective

71
Q

Define inward rectification

A

Current flows in the inward direction more easily thatn the outward direction

72
Q

If the energy profile of an ion has a very deep well, what will this mean?

A

The ion will bind with high affinity in the pore and stay there, blocking the channel

73
Q

What are four properties of calcium channels?

A

1) The ability to distinguish between sodium and calcium
2) High calcium selectivity and flux through thr channel
3) some other divalent ions permeate and others block the channel
4) In the absence of calcium, the channel is permeable to monovalent cations

74
Q

Why are barium currents through calcium channels larger that calcium currents?

A

Calcium binds to the channel better than barium

75
Q

Why does calcium current prevent monovalent cations from passing through the calcium channel?

A

Calcium binds to channel for a while, blocking monovalent cation flux

76
Q

What effect does cadmium have on L-type calcium channels?

A

It binds to the channel and stays there blocking it

77
Q

What part of the α1 subunit of the calcium channel forms the pore? And what amino acids make up this pore?

A
H5 region (half membrane spanning loop between TM domain 5 and 6)
Glutamate (negatively charged)
78
Q

What part of the α1 subunit of the calcium channel forms the voltage sensor?

A

TM domain 4

79
Q

What consequences can mutations in the glutamate ring in the calcium channel pore have?

A

It can alter the calcium block of monovalent current

80
Q

How is it possible that calcium channels select calcium over sodium at a ratio of 1000:1 despite both ions being the same size?

A

Calcium channels can hold more than one ion at a time. When one calcium ion is present, it binds with high affinity blocking sodium entry. If two calcium ions are present, they bind with lower affinity allowing flow of calcium through the channel

81
Q

What is the molecular basis of potassium selectivity?

A

Potassium in selectivity filter must shed its hydration shell to squeeze through - precise spacing of carbonyl oxygens ensures that potassium is coordinate perfectly (the hydration shell has the same shape as the carbonyl oxygens) whereas sodium is too small.

82
Q

How does depolarisation open voltage gated channels?

A

Charged residues within the voltage field experience a force as the membrane potential is altered

83
Q

What is N-type inactivation?

A

A type of ion channel block whereby the N-terminal tail blocks the open channel

84
Q

What is TEA+ used for?

A

Block potassium channels

85
Q

How can block by TEA+ be voltage dependent?

A

The binding site for TEA+ is located in the centre of the potassium channel meaning that it is within the voltage field

86
Q

Name two cases of channels being blocked by intracellular ions?

A

1) Magnesium ions cause a voltage dependent block of some potassium channels leading to rectification
2) Polyamine ions cause a voltage dependent block of potassium channels leading to the properties of a strong inward rectifier

87
Q

Why is channel block so voltage dependent?

A

The channel can hold n charged ions before it reaches the selectivity filter. Therefore a movement of n charges across the electrical field is required to move the ion blocker into place where it can block the channel (e.g. spermine displaces up to five potassium ions from the pore to get to its deep blocking site).

88
Q

What is the mechanism of inward rectification?

A

Ion channel block. e.g. Spermine (a polyamine) cannot reach blocking site when potassium flows outwards, but when potassium flow is in the inwards direction, it can reach blocking site

89
Q

How can you isolate the calcium current in smooth muscle cells?

A

Use patch pipette measure whole cell recordings. Current recorded with potassium in pipette (mixed current). Current recorded with Cs+ (cesium) - blocks potassium current - gives calcium current. Subtract calcium current from mixed current to get potassium current.

90
Q

What are the three types of calcium activated potassium channels?

A

1) Large conductance calcium activated potassium channels (Bk)
2) Intermediate conductance calcium activated potassium channels (Ik)
3) Small conductance calcium activated potassium channels (Sk)

91
Q

What are five general properties of Bk channels?

A

1) Activated by depolarisation (voltage gated)
2) Activated by increase in internal [calcium]
3) Single channel conductance is large
4) Classed with the voltage gated potassium channels
5) Can have both α and β subunits

92
Q

What is the structure of Bk channels?

A

Four subunits make a functional Bk channel. β subunit likely to interact with the N-terminal of the α subunit. S4 region has positively charged amino acid residues contributing to voltage sensitivity. Calcium bowl has at least one calcium binding site (high affinity).

93
Q

What are Bk channels activated by?

A

Depolarisation and calcium

94
Q

How do β subunits affect the Bkα channel?

A

They cause alterations in the voltage and calcium dependent activation and change the rates of activation and some induce inactivation of Bk channels

95
Q

What are STOCs and how do they occur?

A

Spontaneous transient outward current resulting from activation of Sk, Ik or Bk (mostly Bk) channels. Release of calcium from RyRs is enough to cause STOCs

96
Q

What are STICs and how do they occur?

A

Spontaneous transient inward current resulting from activation of e.g. chloride channels

97
Q

What effect does the β1 subunit of Bk channels have on STOC amplitude and why?

A

Increases STOC amplitude because it causes the channels to be open more frequently

98
Q

The heart is said to be two functional syncitya joined together; what does this mean?

A

Cardiac muscle cells are electrically connected by gap junctions and thus the entire myocardium behaves as as single unit

99
Q

Why does the AVN cause a slight delay in electrical propagation between atria and ventricles?

A

Gives enough delay that atria can fill ventricles before they contract

100
Q

What is different about SA nodal action potential upstroke?

A

Upstroke is slow as it is carried by calcium current rather than sodium current

101
Q

What four factors effect regional conduction velocity?

A

1) Cell diameter
2) Membrane resistance
3) Rate of depolarisation
4) Electrical coupling to neighbouring cells

102
Q

How is a gap junction formed?

A

Six connexins form a connexon. Two connexons form a channel.

103
Q

What is the function of intercalated discs?

A

Provide a greater surface area for gap junctions

104
Q

What are the three main connexins in cardiac tissue?

A

Cx43 - contractile
Cx45 - conduction
Cx40
(Different connexons expressed in different regions of the heart - affects conduction)

105
Q

In gene knockout studies, how do you study genes that are involved in development? (Normal KO would produce unviable animals)

A

Create conditional KO animals. For example (mice):

1) Cx43 gene floxed (loxP sites added to either end of the Cx43 gene) in one mouse.
2) Cre-recombinase inserted into MHCα promoter (only gets switched on in adult ventriculat myocytes) to produce MHCα Cre mouse.
3) Breed togther
4) MHCαCre:Cx43flox/flox mouse - cre recombinase gets upregulated in adults and cuts out DNA between loxP sites thereby deleting Cx43 gene

106
Q

What is the consequence of Cx43 conditional KO mice?

A

Mice die from ventricular arrhythmias and sudden death (prone to ischaemic insult). Conduction across myocardium is slower also (other connexons must be present as there is still conduction)

107
Q

What gap junction modifications occur in acute cardiac ischaemia and what causes the ischaemia?

A

Gap junction connexins redistribute to lateral side of cell away from the intercalated discs through phosphorylation and become closed hemichannels. Conduction is slowed and not synchronous. Ischaemia is due to sudden, rapid reduction on blood supply

108
Q

How does the anti-arrythmic peptide rotagaptide exert protective effects for people with acute cardiac ischaemia?

A

Downstream changes in Cx43 phosphorylation

109
Q

Why does the ventricular action potential have slow repolarisation?

A

Sodium and calcium channels cannot reactivate which prevents asynchronous contraction - it allows ventricular relaxation and refilling

110
Q

How is stable resting ventricular membrane potential achieved?

A

Voltage dependence of Iki means high conductance to potassium at resting potentials keeps resting membrane potential close to potassium equilibrium potential

111
Q

How does the ventricular myocyte action potential plateau come about?

A

Balance between depolarising (inward) and repolarising (outward) currents. Long inward calcium current and small, delayed outwards potassium current. Eventually potassium current tips the balance towards repolarisation but this takes time which is why the plateau is long

112
Q

What is a major difference between calcium currents and sodium currents?

A

Calcium currents are smaller but longer lasting, sodium currents are bigger but very short

113
Q

What is the issue with using ruptured patch recordings and how can this be avoided?

A

Issue: solution in patch pipette and cytoplasm exchange - important contents washed out of patch.
Solution: Instead, use perforated patch - ionophores insert into membrane making holes that allow ions through but not other molecules (e.g. 2nd messengers)

114
Q

What is weird about hERG (Ikr) channels?

A

Passes current better at more negative potentials. Activation time course is slow. Inactivation is fast. (opposite to most channels)