Muscle cells

Question 1

hypertension

Answer 1

high blood pressure

Question 2

Cardiac output

Answer 2

amount of blood pumped by each ventricle per minute

CO = heart rate x stroke volume

NB: left and right ventricles have the same cardiac output (CO)!

at rest: 5L/min, 70 beats/min, 70mL/beat

Question 3

Ion channels

Answer 3

voltage-dependent membrane-imbedded proteins that pass a particular ion, usually selectively, in one direction (dependent on the electrical and chemical gradients) or can be activated by a ligand.

Ca2+ channels (L-type and T-type)
K+ channels (at least 15 types in heart)
Na+ channels (one major type)

Question 4

Pumps

Answer 4

ATP-dependent and voltage-independent membrane-imbedded proteins responsible for the movement of ions against a chemical gradient (and possibly an electrical gradient).

Question 5

Exchangers

Answer 5

voltage-independent & ATP-independent membrane-imbedded proteins that pass usually two different species of ions, uni- or bi-directionally (affected by chemical and electrical gradients)

Exchanger uses a favourable gradient (eg. Na+) to move another ions (eg. Ca2+) against its gradient. This avoids the use of ATP.

Question 6

Channel activation
(eg. Na+ channel)

Answer 6

S4 region of channel contains highly charged amino acids, and physically moves in response to voltage change. This causes opening of channel (but we don’t yet know how).

Movement of S4 exposes residues to extracellular solution, and generates a ‘gating current’, which can be measured.

Mutations in S4 that reduce the # of charges reduce the gating current and make the voltage dependence of Na conductance (i.e. probability of channel opening) a less steep function of voltage.

Question 7

(voltage-activated) Ion channels
Ion channels can be in three different states (or transitions).

Answer 7

Activated, inactivated and reprimed

Inactivation – channel stops passing current, even with maintained depolarization

The channels movement through the phases is largely voltage-dependent, but in many cases is also time-dependent (when moving from activated to inactivated).

Question 8

Cardiac muscle has special structures that are responsible for its characteristic contractile properties

Answer 8

adjacent cardiac cells are interlocked (intercalated discs) & structures that anchor membranes together (desmosomes) & allow ions to move between cells (gap junctions)

So cardiac muscle cells are electrically coupled & function as a single coordinated unit “functional syncytium”

Note: No gap junctions between atrial and ventricular cells, plus these are separated by electrically non-conductive fibrous skeleton that surrounds the AV valves

Question 9

autorhythmicity

Answer 9

the heart generates action potentials itself

there are different cell types in the myocardium
 contractile cells (most of cardiac cells) - mechanical work
 conducting & autorhythmic cells (~1%) - APs

Question 10

Nernst Potential

Answer 10

Vm (mV) = (RT/F).ln([K+out]/[K+in])

Question 11

Excitation-contraction coupling
in cardiac cells

Answer 11

Absolute refractory period = 0.25-0.30 s

Relative refractory period = 0.05 s

Question 12

Electrical Conduction
ensures efficient pumping

Answer 12

1. Atrial excitation & contraction is
   completed before onset of ventricular events
2. Electrical transmission to the ventricles
3. Ventricular excitation & contraction occurs

Question 13

Electrocardiography

Answer 13

ECG is the recording of that part of the electrical activity induced in body fluids by the cardiac impulse that reaches the body surface, not a direct recording of the electrical activity of the heart.

Question 14

The Cardiac Cycle

Answer 14

is the period between one heartbeat and the next

systole = contraction (ejection of blood)

diastole = relaxation (filling with blood)

Electrical activity precedes mechanical activity

Blood flows from region high pressure to low pressure

Valves open when there is greater pressure behind them

A highly specific sequence of
chamber contraction and pressure changes is required

Question 15

Length of Cardiac Cycle

Answer 15

Cardiac cycle = 0.8 s (@ 75 beats/min)

Ventricular systole = 0.3 s

Ventricular diastole = 0.5 s

Increased heart rate 75 to 180 b/min
reduces V diastole about 75%
ie. from 500 ms to 125 ms

Question 16

The regulation of Cardiac Output

Answer 16

Controlled by changing HR and/or SV

Question 17

Regulation of Heart Rate

Answer 17

Effect of Parasympathetic NS

Acetylcholine slows the closure of K channels (fast acting):
Increases resting leakage K -> hyperpolarisation
Opposes normal decrease K permeability -> slower depol
Also slows opening Ca channels -> slower depol

Vagus innervation mainly SA and AV nodes

SA node = overall slows pacemaker activity = decrease HR

AV node = decreases node excitability = longer AV delay

Other effects of PSNS on heart:
Atrial contraction: weakens
Ventricular contraction: weakens

The combination of brief latency period and the rapid decay of the response allow vagus nerves to exert a beat-to-beat control on heart rate.

Noradrenaline decreases K permeability:
accelerates inactivation of K channels -> rapid drift to
threshold -> increased depolarisation rate
Plus NAd increases inward Ca current

Sympathetic nerves innervate SA and AV nodes
and non-pacemaker contractile cells

SA node = overall increases pacemaker activity =  HR

AV node = increases conduction velocity = shorter AV delay

Atrial & ventricular contraction = increases

Ventricular conduction = increased excitability, velocity

Question 18

Calcium signalling

Answer 18

• Calcium ions (Ca2+) impact on nearly every aspect of cellular life.
• It has a highly localised nature of action and mediates signal transduction with specific roles in excitability, exocytosis, motility, apoptosis and transcription.

Question 19

How do cells work within their environment?

Answer 19

The cell membrane senses the world by differentiating charge.

To adapt to changing environments, cells must signal.
This requires second messengers (eg. Ca2+) whose concentration varies in time and space.

Ca2+ has two positive charges that give it a high affinity for binding to negatively charged proteins.

Question 20

Structural hierarchy of skeletal muscle

Answer 20

Muscle
Muscle Fibres
Muscle Fiber
Myofibril
Sarcomere

Question 21

Sarcomere

Answer 21

functional unit of striated muscle
(contractile proteins only shown)

diagram

Question 22

points about Ca2+ signalling

Answer 22

1. The free Ca2+ concentration is always a very small portion (typically < 1%) of the total calcium concentration.
2. This means Ca2+ is heavily buffered in the cell by binding to proteins.

Ca2+ binding to protein can cause a conformational and functional change

Major Ca2+ binding sites in the cell:
1. Troponin C (in the cytoplasm).
2. Parvalbumin (in the cytoplasm)
3. Membrane-imbedded proteins (both sides of the membrane).
4. Calsequestrin (inside the sarcoplasmic reticulum).

The majority of the cell’s calcium is bound to calsequestrin inside the SR, the Ca2+ store of the cell.