Cardiovascular Control 1 Flashcards
How is resting membrane potential established?
membrane more permeable to K ions so diffuse down [] gradient carrying positive charge with them
not permeable to negative charge so incident chamber becomes more positive
electrical gradient opposes concentration gradient and equilibrium reached when they equal
What is used to predict equilibrium potentials?
Example for K (Ek)
Nerst equation - depends on flow of ion out of cell
[K] outside = 5mM
[K] inside = 120mM
Ek = -80mV (near RMP of ventricular myocyte)
K[] maintained by Na/K ATPase that pumps K into cell against [] gradient
Ek = RT/ZF ln[K]o/[K]i
What is the resting membrane potential (diastole)?
K+ equilibrium potential (Ek)
because at rest (diastole) the membrane is only permeable to K
What is the equilibrium potential for Na? ENa
[Na]o = 140mM [Na]i = 10mM ENa = +66mV
When does membrane potential = ENa?
during upstroke of action potential
What is the Goldman-Hodgkin-Katz Equation?
membrane potential is better described when the relative permeability of all ions is considered simultaneously
E(mv) = 61log Px[x]i + y + z
—————————
Px[X]o + y + z
What can change membrane potential?
permeability of membrane to ions
What is RMP for a ventricular myocyte?
-90mV
RMP depends on flow of K out of the cell
IK1 flows during diastole to stabilise the RMP - membrane is more negative
Why does depolarisation not reach equilibrium potential of Na in nerve cell?
Na+ channels inactivate as potential becomes positive to stop the outflow of Na
K permeability increases so positive charge flows out of the cell to restore membrane potential
What is the absolute refractory period?
time where no action potential initiated regardless of stimulus intensity
What is relative refractory period?
period after ARP where action potential elicited if stimulus strength is larger than normal
What is the difference between nerve and cardiac AP?
nerve shorter (2-3ms) cardiac (200-300ms) duration of the action potential controls the duration of heart contraction so for the heart to be an effective pump it must have a long and slow contraction
What determines cardiac action potential at rest?
K+
membrane is largely permeable to K to stabilise membrane potential
What physiological mechanism reduces the risk of arrhythmia in cardiomyocytes?
a large stimulus is required to excite the cell
What happens during Phase 0?
= UPSTROKE
AP causes a large change in Na permeability of the cardiomyocyte
Influx of Na
What happens during Phase 1?
= EARLY REPOLARISATION
Large intracellular Na inactivates Na channels and reduces PNa - Na channels enter ARP
Increase in permeability to K
K leaves the cell causing notch in graph (TO/ transient outward potassium current starts)
What happens during Phase 2?
= PLATEAU
Large intracellular Na[] increases PCa early in plateau via LTCC
Influx of Ca triggers CICR release from Ca stored for contraction
Increase Ca intracellular and efflux of K maintains plateau at 0mV to allow prolonged AP
What happens during Phase 3?
= REPOLARISATION
PCa decreases and PK increases (slow and small)
LTCC inactivated slowly
Repolarisation by normal K channel causes IK1 K channels (other subtype) to open
What is the full recovery time?
time at which a normal AP is elicited with a normal stimulus
What is the significance of refractory periods?
Recovery time is caused by Na inactivation
Na channels reactivate as the membrane repolarises
RP is good for the heart to allow it to fill before next stimulus causes a contraction
What is the difference in RP between skeletal and cardiac muscle?
Skeletal - repolarisation occurs early in contraction phase so restimulation and summation of contraction is possible and a second AP can quickly be stimulated
Cardiac - long RP so you cannot re-excite the muscle until the contraction is already well underway
Muscle cannot be tetanised
What is tetanus?
sustained contraction following series of stimuli
Which K channel is responsible for fully repolarising the cell?
IK1
large current that stabilises the membrane potential to reduce the risk arrhythmia. Gradual activation of K currents (K outward of cell) balances and overcomes Ca influx
activated once the cell is partially repolarised
during RRP
How to reduce contraction of smooth muscle to prevent hypertension?
Ca influx blocked by dihydropyridine Ca channel antagonists that bind to LTCC and block it
NIFEDIPINE, NITRENDIPINE, NISOLDIPINE
How are Ca channel antagonists used in cardiac muscle?
block LTCC to reduce rate of upstroke
decrease strength of contraction
decrease HR
Why do different parts of the heart have different AP shapes?
different ion currents flow
different ion channel expression in the cell membrane
graphs combined produce PQRST wave (depolarisation towards +ve electrode = upwards deflection, away = downwards deflection)
Repolarising effects are the opposite
What properties of myocytes allow an intrinsic heart beat?
spontaneously generate
propagate electrical activity in coordinated way via specialised conduction system to excite cells from apex upwards
has own intrinsic pacemaker (cells of SAN)
Where is the SAN located?
where the SVC and IVC meet the right atrium
What does intrinsic heart beat mean? What is the heart extrinsic nerve supply?
heart beats independently of nerve supply
autonomic extrinsic nerve supply modifies and controls intrinsic beating of the heart
What is the action potential of the SAN?
- produce own AP
- do not have IK1 channels therefore SAN cells do not have a stable MP
- upstroke caused by Ca influx via LTCC (not Na)
- also contain TTCC that activate at more negative MP than LTCC
- Ito current is very small
- IF/Pacemaker current present
- repolarisation by gradual inactivation of Ca channel and increase K permeability
What do contractile cells do ?
depolarise upon stimulation
What nervous supply affects SAN?
sympathetic/para nerves synapse with SAN cells
transmitter released has different effects on the SAN
affects the rate of SAN firing that is responsible for modulating heart rate
How does sympathetic stimulation to SAN work?
adrenaline
increase HR (chronotropy)
increase contractility (inotropy)
steeper pacemaker potential so threshold potential reached more quickly
How does parasympathetic stimulation to SAN work?
acetylcholine
decrease gradient of pacemaker potential so TP reached more slowly
decrease speed of depolarisation to threshold of SAN cell - fire less frequently - HR decreases
How does the CNS connect to the SAN?
from: regulatory and vasomotor centres in medulla of brain
parasympathetic is via vagus nerve to SAN
sympathetic nerves from centre to SAN/ventricular tissue
What is the structure and function of the SAN?
below epicardial surface at boundary of SVC and RA
- cells spontaneously depolarise
- heart generates own rhythm (autorhythmicity)
- SAN is a specialised cluster of autorhythmic cells
What are internodal fibres?
rapid conduction tracts to AVN to stimulate atrial myocardium
What is the AVN?
specialised cells that delay the wave of excitation and insulate from superior ventricular myocardium
allows ventricles to fill (-100ms)
What is the Bundle of His?
splits into 2 branch bundles
rapid conduction of insulated excitatory wave
What are Purkinje fibres?
conduct action potential at 6x velocity of myocardium
propagate impulse across ventricular myocardium
Describe the process of impulse propagation?
cardiac AP is propagated by the passive spread of current and existence of threshold over which cell can generate own AP
Gap junctions reduce membrane resistance
- current easily leaks from cell to cell
- connexins form tubes linking cells (connexons)
- GJs located at intercalated discs
What is responsible for cardiac muscle relaxation?
sarcoplasmic ER Ca ATPase pumps Ca from cytoplasm into SR
