T3 L18: Molecular control of the heart Flashcards
What is the difference between extrinsic and intrinsic regulation of force contraction in the heart?
Intrinsic is at the cellular level, extrinsic involves compounds from other cells and making the cross bridge formation stronger
What does greater overlap of sarcomeres cause?
Stronger force of contraction
How quick is the isolated/denervated heart rate?
100 beats per minute
Why is the normal resting heart rate lower than the isolated denervated heart rate?
Normal heart rate is toned by parasympathetic stimulation
What effect does noradrenaline have on the funny current?
It increases the funny current. The pacemaker potential will increase via beta-receptors
What do pacemaker cells do?
Control the rate of contraction of cardiomyocytes
What does an increase in Ca2+ do to cardiomyocytes?
Increases force of contraction
What does an increase in K+ do to cardiomyocytes?
It shortens the action potential so allows a faster heart rate
When do HCN channels open and what do they do?
They open when the membrane becomes negative and they help control the slope of the pacemaker potential
What do alpha-1 adrenergic receptors do?
Work using the Gq pathway to increase Ca2+ and cause vasoconstriction
What do alpha-2 adrenergic receptors do?
Work using Gi pathway to increase glucagon and decrease insulin
What do beta-receptors do?
Work using the Gs pathway to increase heart contractility, heart rate, bronchodilation
What type of stimulation does the vagus nerve carry?
Parasympathetic
What effect does vagal stimulation have on heart rate and how?
It releases ACh to increase K+ which hyperpolarises the membrane and slows down heart rate
What does atropine do?
It blocks vagal stimulation so heart rate can increase
What ion is involved in delayed rectifier channels in the heart?
K+
What ion is involved in inward rectifier channels in the heart?
K+
What is E-C coupling?
The link between excitation and the consequent huge influx in cytosolic Ca2+
What do RyR do?
Release Ca2+ from the sarcoplasmic reticulum
What does SERCA do?
Pumps Ca2+ back into the sarcoplasmic reticulum
What can Ca2+ overload cause?
Ectopic beats and arrhythmias because Ca2+ spill out of the SR
What does the drug Amlodipine do and what is it used for?
Its a Ca2+ blocker used to treat angina and arrhythmias
What does the drug Verapamil do and what is it used to treat?
Ca2+ blockers used for arrhythmias because it slows down nodal rate
What does the drug Diltiazem do and what is it used to treat?
A Ca2+ blocker used to treat angina and arrhythmia because it slows down nodal rate and reduces workload
What does the drug Digoxin do?
It increases stroke volume and contractility so is used for heart failure. It works by inhibiting Na+/K+ channels and by stimulating the vagus nerve
What is the preferred treatment for heart failure?
Beta-blockers because there a lower mortality rate compared to Digoxin
Where is NO released from?
The endothelium
What 2 things does the endothelium detect?
Stretch and plasma proteins
Which protein initiates VSMC (vascular smooth muscle cell) contraction?
Myosin light chain kinase (MLCK)
How does MLCK work?
It phosphorylates mysoin at its light chain
What is MLCK activated by?
Calcium calmodulin (Ca2+ bound to protein)
What is the drug Glyceryl Trinitrate (GTN) used for?
For vasodilatation because it degrades to NO within the body but tolerance can be built so its taken in pulses
What does Bradykinin do?
It vasodilates but constricts bronchi and GI tract smooth muscle
Which drugs prevent degradation of bradykinin?
ACE inhibitors. They cause a dry cough when the bradykinin accumulates
When would Troponin (Tn) be released?
Released from cardiomyocytes during necrosis
What increases Creatine Kinase (CK)?
Released from cardiomyocytes during necrosis
Wat increases C reactive protein (CRP)?
Increases during inflammation
