Electrical and Molecular Mechanism & Autonomic Control of CVS Flashcards
What is the resting membrane potential of cardiomyocytes set by and how?
K+ permeability - the ions move out of the cell down their concentration gradient and the small movement of ions makes the inside negative with respect to the outside - as charge builds up, the electrical gradient is established.
Does the resting membrane potential equal the equilibrium potential of potassium, why?
No, equilibrium potential of potassium will exist when there’s no net movement of potassium, but the cardiomyocytes membrane has a very small permeability to other ion species.
What does it mean for cardiomyocytes to be electrically active?
They fire action potentials, which trigger and increase in intracellular Ca2+, which is required for actin-myosin interaction, for contraction. Action potentials in the heart are much longer than in neuronal axons.
What are the 4 stages of cardiomyocytes’ action potentials?
Include voltages and timings.
- Opening of V-gated Na+ channels leads to influx and upstroke, from -70 to +20mV.
- Initial depolarisation due to transient V-gated K+ channels causing efflux (Na+ channels inactivated) to just above 0mv.
- Opening of L-type VOCC, result in plateau (CICR- crosses 0) with balance of K+ efflux for 100ms.
- Repolarisation as Ca2+ channels inactivate and K+ efflux continues back to -85 mV.
From 200-450ms - shape.
How come pacemaker cells at the SAN don’t need nerve impulses to stimulate them?
Specialised mulches don’t sit at rest.
The first stage in the SAN action potential involves the pacemaker current, which is what?
What’s the involvement of HCN channels (what does it stand for)?
Aka funny current - initial slope to threshold from -60 to -40mV - influx of Na+ through HCN channels.
Hyperpolarisation-activated Cyclic Nucleotide-gated channels.
What happens when the pacemaker potential reaches threshold - the rest of the SAN action potential?
Opening of L-type Ca2+ channels causes influx and depolarisation (CICR) up to +15mV ish, then opening of V-gated K+ channels, with effluvia and repolarisation. The pacemaker potential/funny current is reactivated in membrane potential falls lower than -50mV. The whole thing takes 800ms.
Action potential waveform varies throughout the heart, why does the SAN set the rhythm/act as the pacemaker?
Although other parts of the conducting system also have automaticity, they are slower to depolarise.
The triggering of a single action potential, which spreads through the heart is responsible for contraction. What's it called when: Action potentials are too slow Action potentials are too quick Action potentials fail Electrical activity becomes random?
Bradycardia
Tachycardia
Asystole
Fibrillation - causes loss of cardiac output.
What are the plasma concentration ranges of normal potassium, in hyperkalaemia and in hypokalaemia?
Normal = 3.5-5.5 mmol/L
Hyperkalaemia > 5.5mmol/L mild is up to 5.9, moderate is up to 6.4 and severe is above that
Hypokalaemia < 3.5mmol/L
Why are cardiomyocytes so sensitive to changes in the concentration of potassium?
Potassium permeability dominates the resting membrane potential of cardiomyocytes and the heart has multiple types of K+ channel, some of which may behave peculiarly.
Explain the effects of hyperkalaemia including some risks.
There is a decreased driving force for K+ to leave the cells, so they are less negative inside - the equilibrium of potassium is less negative. This means that myocytes are depolarised and the upstroke of the action potential is slower - some Na+ channels are inactivated with slight depolarisation.
Risks: asystole, initial increase in excitability. Depends on extent and how quick.
How might hyperkalaemia be treated?
Calcium gluconate or insulin + glucose - won’t work if heart has already stopped.
What happens in hypokalaemia and what are the problems?
Lengthens action potential, so delays hyperpolarisation. Problems include longer action potentials leading to Early After Depolarisations (EADs), which can lead to oscillations in membrane potential, which can result in ventricular fibrillation and a subsequent loss of cardiac output - more likely o have arrhythmias if preexisting heart condition.
Briefly describe excitation-contraction coupling in cardiac muscle.
Depolarisation opens L-type Ca2+ channels in the T-tubule system - localised Ca2+ entry triggers CICR from RyR in SR - close link between 2 types of Ca2+ channels -25% Ca2+ entry across sarcolemma and 75% from SR. As with skeletal muscle, Ca2+ binds to troponinC, conformational change shifts tropomyosin to reveal myosin binding site on actin filament - sliding filament mechanism.
Cardiac muocyte relaxation - Ca2+ returns to resting levels by SERCA, NCX & sarcolemma Ca2+ATPase.
What is the tone of blood vessels controlled by?
The contraction and relaxation of vascular smooth muscle cells (in tunica media present in arteries, arterioles and veins).
Briefly describe excitation-contraction coupling in vascular smooth muscle.
Ca2+ binds to calmodulin and the complex activates MLCK, which phosphorylases the regulatory myosin light chain to permit actin interaction. Relaxation occurs as MLC phosphatase dephosphorylates MLC. MLCK itself may be phosphorylated by PKA, to inhibit it and therefore inhibit contraction.
This occurs at alpha1 receptors - G alpha q - phospholipase C –> IP3 (Ca2+ release) + DAG (PKA).
Wants the purpose of the autonomic nervous system?
It’s important for regulating many physiological functions - homeostasis, coordinating the response to stress and is largely outside voluntary control and exerts control over smooth muscle, exocrine secretion and rate and force of heart contraction.
What decides whether a part of the ANS is included in the sympathetic or parasympathetic division?
Anatomical grounds - preganglionic neurones arise from spinal chord - craniosacral/thoracolumbar. Where both the parasympathetic and sympathetic systems both innervate a tissue, they often exert opposite effects.
When are the parasympathetic and sympathetic nervous systems in use?
Sympathetic activity is increased under stressful conditions and parasympathetic activity is more dominant under basal conditions.
Both work together to achieve the balance of homeostasis.
What makes sweat glands and the adrenal medulla exceptions?
At the sweat glands, post ganglionic neurones secrete ACh to act of M3 receptors instead of NA.
Chromatin cells of the adrenal medulla act as post ganglionic neurons, releasing NA into the blood.
How can the sympathetic nervous system exert an effect on the heart and not simultaneously stimulate the GI tract?
Sympathetic drive to different tissues is independently regulated, so rather than a coordinated response triggered by fight or flight, sympathetic activity can be separate.
What does the ANS control in the CVS and what are its limits?
It controls the heart rate, force of contraction of the heart, peripheral resistance of blood vessels (arteriolar contraction) and venoconstriction.
It does not initial electrical activity in the heart, as a denervated heart still beats, but faster (100bpm), as the heart at rest is normally under vagal influence.
Where does parasympathetic input to the heart come from and go to?
Preganglionic fibres originate from the 10th/X cranial nerve - Vagus. The synapse with post ganglionic cells is on the epicardial surface or within the walls of the heart - at the AVN or SAN more likely.
