Cardiovascular control 1 Flashcards
Describe the membrane potential when there is no movement of ions
There is no membrane potential
Why do different cells have different shapes for their action potentials
Due to different currents flowing.
Describe the potassium hypothesis
▪ The membrane is more permeable to potassium ions than anything else and these can diffuse down a concentration gradient, carrying positive charge with them. ▪ As they move, the incident chamber becomes increasingly positive relate to the other chamber (as other negative ions cannot move due to the barrier being impermeable to them). ▪ The electrical gradient then directly opposes the concentration gradient and eventually you get a point when the electrical gradient = the concentration gradient and equilibrium is achieved
What is the importance of the Na+/K+ pump
Without it, concentration gradients would collapse, signalling mechanisms and cardiac contraction would fail.
During the upstroke of AP, when the membrane is only permeable to sodium, will the sodium equilibrium potential be reached
No, due to the inactivation of the Na+ channels
Describe the movement of K+ ions at equilibrium
At equilibrium, K+ ions move randomly back and forth
The driving force, the difference between the concentration and the electrical gradient, is zero at equilibrium
Explain how we can calculate resting membrane potential
If the membrane is only permeable to K+ at rest (diastole) then the potential across it will equal the K+ equilibrium potential, (EK)
Equilibrium potential is calculated by solving the Nernst equation for K +
What is the membrane potential better described by
In reality membrane potential is better described by the Goldman-Hodgkin-Katz equation
Takes into account the relative permeabilities of several ions simultaneously
What controls the duration and strength of contraction of the heart
The duration of the action potential.
Describe how the cardiac action potential compares with the nerve action potential
Compared with nerves the cardiac action potential is very long (200-300 ms vs. 2-3 ms)
Why is the duration of the cardiac action potential important
Long, slow contraction is required to produce an effective pump
Describe what is meant by absolute refractory period
Absolute refractory period (ARP) = time during which no action potential can be initiated regardless of stimulus intensity
Describe what is meant by relative refractory period
Relative refractory period = period after ARP where an AP can be elicited but only with stimulus strength larger than normal.
What are refractory period caused by
Refractory periods are caused by Na+ channel inactivation
Na+ channels recover from inactivation as the membrane repolarises
As it repolarises more, more Na+ channels are activated, hence the likelihood of generating an action potential increases (larger depolarisation from the same stimulus).
What is meant by full recovery time
Full recovery time (FRT) = the time at which a normal AP can be elicited with a normal AP.
At what membrane potential does full recovery time occur
Around -85mV.
What is meant by tetany
Series of contractions following a series of stimuli.
What is the importance of the long refractory period seen in cardiac muscle cells
In cardiac muscle, the long refractory period means it is not possible to re-excite the muscle until the process of contraction is well underway hence cardiac muscle cannot be tetanised
it also allows the heart to fill fully before the arrival of the next stimulus.
What are the phases of the action potential in cardiac muscle
Phase 0 - upstroke Phase 1- Early repolarisation Phase 2- Plateau Phase 3- Repolarisation Phase 4- Resting membrane potential.
What is the resting membrane potential determined by
At rest, membrane potential determined by K+. o Large membrane permeability to K+ stabilises membrane potential reducing risk to arrhythmias by requiring a large stimulus to excite the cells.
What causes the rapid upstroke
Upstroke determined by large increase in membrane to Na+ permeability
What are the two consequences of the increase in permeability to sodium ions
a. Large [Na+] Intracellular inactivates Na channels and thus reduces PNa quickly and this causes a brief increase in PK which gives the characteristic notch on the graph as K leaves the cell. Na channels enter absolute refractory period.
b. Large [Na+] Intracellular also increases PCa early in plateau via LTCC. Influx provides trigger for Ca2+ release from intracellular stores for contraction.
What causes the plateau on the graph
- The Ca2+ intracellular increase combined with the K+ efflux maintains the plateau of the graph.
- Plateau ends when PCa decreases and a slow and small increase in PK occurs.
What causes the repolarisation of the cardiac muscle
- Repolarisation occurs due to inactivation of LTCC and opening of another subtype of K+ channels.
Describe the events that take place during early repolarisation
Inactivation of sodium channels (no further depolarisation) and the transient outward (TO) potassium current starting.
Describe the events that take place during the plateau phase
▪ Large intracellular sodium causes calcium influx which triggers CICR from intracellular stores. ▪ Potassium efflux and calcium influx stabilise the membrane potential around 0mV. ▪ Calcium influx can be blocked by dihydropyridine calcium channel antagonists (bind to LTCC, blocking the channel) such as Nifedipine, Nitrendipine and Nisoldipine.
Describe what happens during the repolarisation phase
▪ Small potassium current starts to activate towards the end of the plateau which begins repolarisation. ▪ As the membrane becomes repolarised (due to efflux of potassium via normal potassium channels), the IK1 potassium channel switches back on (it turns off during depolarisation). ▪ The IK1 current is large and flows during diastole → it acts to stabilise the resting membrane potential and reduce risk of arrhythmia.
Describe the IK1 channels
Large K+ current (IK1) that is inactive during the plateau starts to flow once the cells have partially repolarised
IK1 is responsible for fully repolarising the cell
Why do different parts of the heart have different action potential shapes
Caused by different ion currents flowing and different ion channel expression in cell membrane
Draw action potentials for the ventricle and the sino-atrial node
See diagram!
Does the SA node have a resting potential
No, it is always oscillating.
Describe the intrinsic properties of the heart
Capable of independent spontaneous generation and coordinated propagation of electrical activity
The heart can beat independently even after being separated from its nerve supply
The extrinsic nerve supply coming from the autonomic nervous system serves to modify and control the intrinsic beating established by the heart
What do the different graph shapes for the action potential in different parts of the heart produce
▪ These graph shapes combined create the iconic PQRST shaped wave.
What causes the small depolarisation seen in the SA node
Sodium influx, different and less rapid sodium channels to that of nerves and cardiac muscle
Also by T-type calcium channels which activate at more negative potentials than L-type
What causes the upstroke in the SA node
There is very little sodium influx into SA node cells, instead, the upstroke is caused by Ca2+ influx. Through L-type calcium channels.
What causes repolarisation in the SA node
Inactivation of L-type calcium channels, increasing permeability to potassium ions.
Which channels are not expressed in the SA node and what is the consequence of this
IK1 channels
Repolarisation is caused by The ITO (transient outward) current which is very small.
Less stable membrane potential, due to lower membrane potential, making it easier to activate again.
What current is present in the SA node
Pacemaker current (If) present
Where else are L-type calcium channels present
Smooth muscle
Ca2+ blockers can be used as anti-hypertensive therapy, preventing smooth muscle contraction and thus decreasing the pressure.
What is the key to controlling the cardiovascular system
Controlling heart rate
Describe the effect of sympathetic stimulation on the heart
With sympathetic stimulation of the heart (e.g. adrenaline), it makes the pacemaker potential (the gradual upward slope before the -40mV line) steeper
This means threshold potential is reached more quickly.
Heart rate increases
Describe the effect of parasympathetic stimulation on the heart
With parasympathetic stimulation (e.g. ACh) there is a decrease in the gradient of pacemaker potential.
Takes longer for membrane potential to meet the threshold thus reducing heart rate.
Where are the cardio regulatory and vasomotor centres found
In the medulla of the brainstem.
What does SNS innervation increase
SNS innervation increases heart rate (chronotropy) and contractility (Inotropy)
Describe the SA node
SA node lies just below the epicardial surface at
the boundary between the right atrium and the superior vena cava
The specialised cells that comprise the node mark the start of the conduction pathway
They spontaneously depolarise which allows the heart to generate its own rhythm (autorhythmicity)
What are the 4 parts of the conduction system of the heart
Sinoatrial Node
Inter-nodal Fibre Bundles.
Atrioventricular Node
Ventricular bundles
What is meant by the SA node
Specialised cluster of autorhythmic cells
Describe the inter-nodal fibres
Rapid conduction tracts to stimulate atrial myocardium
Conduct AP to AV-node at a greater velocity than ordinary atrial muscle.
Describe the AV node
Specialised cells to delay wave of excitation and insulate from superior ventricular myocardium- allows atria to fully empty before the ventricles contract
Produces a delay of ~100ms.
Describe the Bundle of His and ventricular bundles
Bundle of his- Rapid conduction cells to transport an insulated wave of excitation
Ventricular fibres- Propagate the impulse across the ventricular myocardium
o Bundle of His descends from AV-node and splits into two bundle branches made of Purkinje fibres o Purkinje Fibres - conduct AP at around 6x the velocity ordinary cardiac muscle and penetrate 1/3rd distance into myocardial wall.
Describe impulse propagation in the heart
Impulses are propagated between cells by the use of gap junctions (cluster at intercalated discs) which have a low resistance. The effect of depolarisation gradually decays.
The propagation of the cardiac action potential is due to a combination of passive spread of current and the existence of a threshold which, once reached, causes the cell to generate its own action potential.
Describe the gap junctions
Gap junctions greatly reduce membrane resistance allowing current to easily leak from one cell to a neighbouring cell.
Intercellular communication and impulse conduction from one cell to the next relies on gap junctions
Gap junctions form at intercalated discs
Many connexons are found within the gap junction.
