The molecular and ionic basis of CV control Flashcards
During intrinsic events, increased cell sensitivity when stretched. Describe the intrinsic regulation of the CVS
Frank-starkling mechanism
Increased contractility
More cross bridges means more everything. Increased overlap of filaments increases force generates and actin filaments have directionality, myosin can only stretch them in 1 direction
Describe the extrinsic regulation of the CVS
Sympathetic stimulation (norepinephrine/noradrenaline)
Faster and stronger contractions
NOT longer duration
Existing cross bridges work harder and faster
HR is maintained around 60bpm by an intervening stimulant as intrinsically the SAN beats at 100bpm. What is this stimulant?
Tonic parasympathetic stimulation
HR is determined by the slope of the pacemaker potential. Which three factors affect this?
- Noradrenaline causes increase in If
This increases the slope via B1-receptor - Noradrenaline increases intrinsic calcium (increases force of contraction)
- Noradrenaline increases delayed K+ rectifiers (shortens AP duration so HR increases)
Describe the funny current
Net current inward (conducts both Na+ in and K + out)
Non-specific monovalent cation channel
The reversal potential of If is -10mv
HCN channel opens when membrane gets more negative (this controls the pacemaker potential slope)
Outline the adrenergic receptors (G coupled)
A1- (Gq)
Phospholipase C -> PIP2, IP3, DAG-> Ca2+-> vasoconstriction in most organs, sweat
A2- (Gi)
Ca2+-> less insulin, more glucagon
Adenyl cyclase converts ATP to cAMP -> less insulin, more glucagon
B- (Gs)
Adenyl cyclase converts ATP to cAMP-> increase heart contraction, HR,skeletal muscle perfusion, lipolysis in adipose
Describe vagal stimulation
Parasympathetic (slow)
ACh -> increases K current, hyper polarise membrane and so decreasing slope of pacemaker potential
ACh-activated K channel and G-coupled proteins and muscuranic (cholingeric)
State the types K+ channels in cardiomyocytes
Inward rectifiers
Delayed rectifiers
ACh-senstive channels
Define and describe the neural AP: after hyperpolarisation
At the end of an AP, the voltage inside becomes more negative than at rest and then it returns to the resting Vm
How?
When Vm below -60mv inward rectifiers open again so more negative than at rest
Delayed rectifies still open (slow to close)
Almost all Na+ channels inactivated
The increased K+ permeability and decreased Na+ permeability leads to membrane potential moving closer to Ek
Describe the effective refractory period
When it become nearly impossible to start a new AP
In cardiomyocytes it lasts for duration of AP
Physiologially protects heart from unwanted extra AP’s between SAN intiated beats
Outline the function of t-tubules and terminal cisternae
A system for storing and releasing Ca2+ in response to Vm
T-tubules are invaginations of plasma membrane into myocyte
Membrane currents can be near contractile machinery
Contiguous with extracellular fluid
Adjacent to SR
T tubules depolarise-> terminal cisternae detects it -> sends to SR
Terminal cisternae= enlarged area of SR specialised for storing and releasing Ca2+
Exist as triad: 1 t-tubule surrounded by terminal cisternae
Define exciting-contraction coupling
The link between the depolarisation of the membrane (with tiny influx of Ca2+) and consequent huge increase in cytosolic Ca2+ -> contraction
Which calcium channel exist in skeletal muscle?
How does it differ in cardiomyocytes
Ryanodine
On SR that releases Ca2+ from intracellular store
Ca2+ channel conformational change doesn’t cause ryanodine to become activated. Instead Ca2+ release from channel triggers intracellular Ca2+ to increase (positive feedback)
What does SERCA do?
In SR membrane
Pumps Ca2+ back into SR (energy costing)
Define calcium overload and state how it may occur?
Excessive intracellular Ca2+, also possible in SR.
It can increase risk of ectopic beats and arrhythmias
It is made worse by fast rates ad sympathetic drive
Increased sympathetic stimulation causes increased EC coupling
