205 L11 Flashcards
Ventricular function
Sarcomere length tension relationship
The —— force that can be generated by skeletal muscle is proportional to the ——– length. The normal operating zone is between 1.8-2.2μm. This is when the maximum — heads are binding to the —- fibres. It’s seen on the graph as a ——- phase. ——- tension only increases when the sarcomeres are at long lengths.
The ——– myocytes operate over a much ——– zone of the sarcomere length than —— muscle, which is due to their ——— - there is much stronger ——– tissue that’s much more restrictive
The ——– stiffness of cardiac muscle limits ———.
The —— myocytes have length dependent activation. This means that the force generated by the cardiac myocyte at different lengths is not just driven by the __-___ interaction. Its also driven by ——-. The cardiac myocyte changes how it deals with the release of ——— at different lengths. This means a smaller change in ——– can give a greater force in cardiac vs skeletal muscle
As length increases there is an ———- sensitivity to ———, so as the myocyte gets ————you get a ———- contractile response for the same input of ———-.
Increased Ca2+ sensitivity of Troponin - C at greater sarcomere lengths
Increased Ca2+entry through stretch activated channels at greater SL
The active force that can be generated by skeletal muscle is proportional to the sarcomere length. The normal operating zone is between 1.8-2.2μm. This is when the maximum myosin heads are binding to the actin fibres. It’s seen on the graph as a plateau phase. Passive tension only increases when the sarcomeres are at long lengths.
The cardiac myocytes operate over a much shorter zone of the sarcomere length than skeletal muscle, which is due to their structure - there is much stronger connective tissue that’s much more restrictive
The passive stiffness of cardiac muscle limits stretch.
The cardiac myocytes have length dependent activation. This means that the force generated by the cardiac myocyte at different lengths is not just driven by the myosin-actin interaction. Its also driven by calcium. The cardiac myocyte changes how it deals with the release of calcium at different lengths. This means a smaller change in calcium can give a greater force in cardiac vs skeletal muscle
As length increases there is an increased sensitivity to calcium, so as the myocyte gets longer you get a greater contractile response for the same input of calcium.
Increased Ca2+ sensitivity of Troponin - C at greater sarcomere lengths
Increased Ca2+entry through stretch activated channels at greater SL
What causes the release of calcium from the sarcoplasmic reticulum in skeletal muscle?
Depolerisation - Sodium influx
What causes the release of calcium from the sarcoplasmic reticulum in cardiac muscle?
Calcium
Myocardial contraction
Action potential (triggered by ——-)
Inward ——— current through ——- channels
——- induces rapid —— release from ——— ——-.
——- binds to ____-__ and starts cycle of ——— interactions for contraction.
Action potential (triggered by -sodium)
Inward calcium current through calcium channels
calcium induces rapid calcium release from sarcoplasmic reticulum.
Calcium binds to Troponin-C and starts cycle of filament interactions for contraction.
Myocardial relaxation
Removal of ——- from cytoplasm via;
——– ——- calcium ATPase (reuptake of calcium)
—— ——- exchange out of cell (Na+ gradient)
———- Ca2+ ATPase
As the calcium concentration drops the calcium will unbind form ___-__ and the contractile proteins will relax.
Removal of calcium from cytoplasm via;
sarcoplasmic reticulum calcium ATPase (reuptake of calcium)
sodium calcium exchange out of cell (Na+ gradient)
sarcolemma Ca2+ ATPase
As the calcium concentration drops the calcium will unbind from Troponin-C and the contractile proteins will relax
Factors influencing the inotropic state of cardiac muscle:
Action Potential duration
↑ AP ——– length –> ↑ —— influx so increased —– release –> ↑ ——- state
External Ion Concentrations
↑ external —— –> ↑ —— because increased ——- –> ↑inotropic state
Lower external —— —> slows ——- —— exchange —> —– accumulates inside –> ↑ inotropic state
Heart rate
———- heart rate—> more —- entry due to more —– —> —– time for calcium —— —-> Ca2+ accumulation –> ↑ inotropic state
Calcium removal is depended on the time that the ——– have to get it out of the cells. The amount of calcium that comes in changes with rate because the number of openings of the channels changes as well with rate.
Neurotransmitters
——- and ———- - SNA, act through beta receptors
Mainly through activation of _-____ pathways adrenergic agonist
Cause phosphorylation of —— channels making them be open for longer
Phosphorylation of phospholamban - increased rate of pump to remove calcium, so that relaxation can occur faster
Cholinergic muscarinic agonist (PNS)
Reduction of [Ca2+]i
decreased inotropic state
Hormones and Drugs
Xanthines (eg. caffeine)
Prevents cAMP breakdown —> increased inotropic state
Cardiac Glycosides (eg. digoxin - short term, the underlying damage continues to accumulate) Inhibit Na+/K+ pump so there is an accumulation of Na inside the cell. Diminished Na+ gradient. Slow Na+/Ca2+ exchange . Ca2+ accumulation inside cell. Increased inotropic state
Calcium channel blockers (eg. verapamil)
reduce Ca2+ entry across sarcolemma => decreased inotropic state
Ischaemia and heart failure
negative inotropic influences. They reduce the ability of the heart to generate force
Action Potential duration
↑ AP plateau length –> ↑ calcium influx so increased calcium release –> ↑ inotropic state
External Ion Concentrations
↑ external calcium –> ↑ influx because increased gradient –> ↑inotropic state
Lower external sodium —> slows sodium calcium exchange —> calcium accumulates inside –> ↑ inotropic state
Heart rate
increased heart rate—> more calcium entry due to more action potentials —> less time for calcium removal —-> Ca2+ accumulation –> ↑ inotropic state
Calcium removal is depended on the time that the channels have to get it out of the cells. The amount of calcium that comes in changes with rate because the number of openings of the channels changes as well with rate.
Neurotransmitters
Adrenaline and nor adrenaline - SNA, act through beta receptors
Mainly through activation of G-protein pathways adrenergic agonist
Cause phosphorylation of calcium channels making them be open for longer
Phosphorylation of phospholamban - increased rate of pump to remove calcium, so that relaxation can occur faster, decreased inotropic state
Cholinergic muscarinic agonist (PNS)
Reduction of [Ca2+]i
decreased inotropic state
Hormones and Drugs
Xanthines (eg. caffeine)
Prevents cAMP breakdown —> increased inotropic state
Cardiac Glycosides (eg. digoxin - short term, the underlying damage continues to accumulate) Inhibit Na+/K+ pump so there is an accumulation of Na inside the cell. Diminished Na+ gradient. Slow Na+/Ca2+ exchange . Ca2+ accumulation inside cell. Increased inotropic state
Calcium channel blockers (eg. verapamil)
reduce Ca2+ entry across sarcolemma => decreased inotropic state
Ischaemia and heart failure
negative inotropic influences. They reduce the ability of the heart to generate force
Factors influencing the inotropic state of cardiac muscle:
Action Potential duration
↑ AP ——– length –> ↑ —— influx so increased —– release –> ↑ ——- state
External Ion Concentrations
↑ external —— –> ↑ —— because increased ——- –> ↑inotropic state
Lower external —— —> slows ——- —— exchange —> —– accumulates inside –> ↑ inotropic state
Heart rate
———- heart rate—> more —- entry due to more —– —> —– time for calcium —— —-> Ca2+ accumulation –> ↑ inotropic state
Calcium removal is depended on the time that the ——– have to get it out of the cells. The amount of calcium that comes in changes with rate because the number of openings of the channels changes as well with rate.
Neurotransmitters
——- and ———- - SNA, act through beta receptors
Mainly through activation of _-____ pathways adrenergic agonist
Cause phosphorylation of —— channels making them be open for longer
Phosphorylation of phospholamban - increased rate of pump to remove calcium, so that relaxation can occur faster
Cholinergic muscarinic agonist (PNS)
Reduction of [Ca2+]i
decreased inotropic state
Hormones and Drugs
Xanthines (eg. caffeine)
Prevents cAMP breakdown —> increased inotropic state
Cardiac Glycosides (eg. digoxin - short term, the underlying damage continues to accumulate) Inhibit Na+/K+ pump so there is an accumulation of Na inside the cell. Diminished Na+ gradient. Slow Na+/Ca2+ exchange . Ca2+ accumulation inside cell. Increased inotropic state
Calcium channel blockers (eg. verapamil)
reduce Ca2+ entry across sarcolemma => decreased inotropic state
Ischaemia and heart failure
negative inotropic influences. They reduce the ability of the heart to generate force
Action Potential duration
↑ AP plateau length –> ↑ calcium influx so increased calcium release –> ↑ inotropic state
External Ion Concentrations
↑ external calcium –> ↑ influx because increased gradient –> ↑inotropic state
Lower external sodium —> slows sodium calcium exchange —> calcium accumulates inside –> ↑ inotropic state
Heart rate
increased heart rate—> more calcium entry due to more action potentials —> less time for calcium removal —-> Ca2+ accumulation –> ↑ inotropic state
Calcium removal is depended on the time that the channels have to get it out of the cells. The amount of calcium that comes in changes with rate because the number of openings of the channels changes as well with rate.
Neurotransmitters
Adrenaline and nor adrenaline - SNA, act through beta receptors
Mainly through activation of G-protein pathways adrenergic agonist
Cause phosphorylation of calcium channels making them be open for longer
Phosphorylation of phospholamban - increased rate of pump to remove calcium, so that relaxation can occur faster, decreased inotropic state
Cholinergic muscarinic agonist (PNS)
Reduction of [Ca2+]i
decreased inotropic state
Hormones and Drugs
Xanthines (eg. caffeine)
Prevents cAMP breakdown —> increased inotropic state
Cardiac Glycosides (eg. digoxin - short term, the underlying damage continues to accumulate) Inhibit Na+/K+ pump so there is an accumulation of Na inside the cell. Diminished Na+ gradient. Slow Na+/Ca2+ exchange . Ca2+ accumulation inside cell. Increased inotropic state
Calcium channel blockers (eg. verapamil)
reduce Ca2+ entry across sarcolemma => decreased inotropic state
Ischaemia and heart failure
negative inotropic influences. They reduce the ability of the heart to generate force
stroke volume = __ -__
SV = End diastolic volume - end systolic volume
Cardiac output = __x__
CO = Heart rate x Stroke volume
Preload = —— —– —–
End diastolic volume
Preload = —— —– —–
End diastolic volume or pressure
Preload is the degree of —- of the muscle just before ——. It determines the —— overlap (length - tension relation) and length dependent activation. As preload increase stroke volume —— and maximum potential pressure ——.
Preload is the degree of stretch of the muscle just before contraction. It determines the filament overlap (length - tension relation) and length dependent activation. As preload increases, stroke volume increases and maximum potential pressure increases.
Preload is the degree of —- of the muscle just before ——. It determines the —— overlap (length - tension relation) and length dependent activation. As preload increase stroke volume —— and maximum potential pressure ——.
Preload is the degree of stretch of the muscle just before contraction. It determines the filament overlap (length - tension relation) and length dependent activation. As preload increases, stroke volume increases and maximum potential pressure increases.
