Lecture 18: Ionic basis of cardiovascular control Flashcards
What comprises the intrinsic regulation of the cardiac muscle contraction?
Frank-Starling relationship
Increased contractility
Longer and stronger
“More crossbridges means more of everything”
What comprises the extrinsic regulation of the cardiac muscle contraction?
Sympathetic stimulation
Faster and stronger
NOT longer duration
“Extant crossbridges work harder and faster”
What is the natural rate of an isolated or denervated heart?
100bpm
What determines heart rate?
Slope of the pacemaker potential
What is the effect of noradrenaline (sympathetic) on the If channel?
Increases activity - net inward current
Increases slope of the pacemaker potential (increases rate)
Acts on Beta1 receptors
What is the effect of noradrenaline (sympathetic) on the Ca channels?
Increases force of contraction
What is the effect of noradrenaline (sympathetic) on the delayed rectifier K channels?
Shortens AP duration
Faster heart rate
What is the HCN channel?
Non-specific monovalent cation channel
Opens when the membrane gets more negative
What is the effect of sympathetic activity of If?
Increases If
What is the reverse potential of If?
-10mV
What pathway is activated by Gq?
PLC - IP3 - DAG
Ca
Vasoconstriction in most organs
What pathway is activated by Gs?
Adenylate cyclase - cAMP
Increase contractility, HR, perfusion of skeletal muscles, lipolysis in adipose tissue
What pathway is deactivated by Gi?
Adenylate cyclase - cAMP
Less insulin, more glucagon
What is the effect of acetylcholine on heart rate?
Vagal - parasympathetic
Increases K current so hyper polarises the membrane
Decreases the slope of the pacemaker potential
Slows HR
What is atropine?
Blocker of muscarinic receptor - blocks vagal slowing of HR
So increases HR
When do the inward rectifier K+ channels open?
When the voltage goes below -60mV
During the AHP which channels are open?
Delayed rectifiers and inward rectifiers are open
Almost all Na channels are inactivated
What is the refractory period?
When there is so much positive current leaving the cell, it is impossible to depolarise it again
At what stage are the delayed rectifier channels closed?
When the membrane is at rest
What is the effective refractory period (ERF)?
When it becomes nearly impossible to start a new action potential
In cardiomyocyte, lasts for duration of AP
Protects the heart from unwanted extra action potentials between SA node initiated heart beats
What are T-tubules?
Invaginations of plasma membrane into myocyte
T tubule depolarises –> terminal Cisterna detects it –> terminal cisterna sends it throughout SR
What is the terminal cisternae?
Enlarged area of SR
Specialised for storing and releasing calcium
What is excitation-contraction coupling?
The link (molecular process) between the depolarisation of the membrane (with a tiny influx of calcium) and the consequent huge increase cytosolic calcium that then leads to contraction
What is the primary control of cardiac muscle contraction?
Diffusion of free calcium into the cytoplasm
Where are large concentrations of calcium stored in the skeletal muscle?
Sarcoplasmic reticulum
What is the name of the receptor on the terminal cisterna that allows the release of large amounts of calcium?
Ryanodine receptors
What is the name of the receptor in the cell membrane that allows a small influx of calcium into the cell to activate the RyR?
DHPR
What is the role of SERCA?
In the SR membrane - pumps calcium back into the SR
Requires ATP
What is the effect of sympathetic stimulation of the EC coupling?
Increases EC coupling
What may be caused by calcium overload?
Risk of ectopic beats and arrhythmia
What is the effect of a DHP calcium channel blocker.
Vasodilates - opposes hypertension
Amlodipine
What is the effect of non-DHP calcium channel blockers?
Anti-anginal and anti-arrhythmic
BUT makes heart failure worse
Verapamil - anti arrhythmic (blocks heart vessels)
Diltazem - anti-anginal and anti arrhythmic (blocks hear and vessel channels)
What is digoxin?
Positive inotropic agent - increases stroke volume and contractility
Works by inhibiting Na/K pump - causes increased Ca in the cytosol
Also stimulates vagus - slows HR
Used for AF
What is the effect of beta2 stimulation on VSMCs in peripheral skeletal muscles?
Cause VSMC relaxation
B2 - cAMP - PKA - p-MLCK (inactive when phosphorylated) - can’t phosphorylate or activate myosin
What is the effect of alpha1 stimulation on VSMCs in core organs and GI tract?
Smooth muscle contraction
A1 - PLC - IP3 - Ca - CaM - MLCK (activate when bound to Ca-CaM) - p-myosin
What is bradykinin?
Peptide hormone that loosens capillaries and blood vessels
Vasodilator - stimulates NO production in endothelium
Increases capillary permeability - increases saliva production
What is the effect of ACE inhibitors on bradykinin?
ACE inhibitors prevent degradation of bradykinin - causes dry cough
When is creatinine kinase released from myocytes?
During necrosis
When is CRP released?
Increased in response to inflammation
When is troponin released from cardiomyocytes?
During necrosis - elevated during AMI but not during unstable angina
