Cardiac Contractility and Depolarization

• The primary role of the heart is to circulate blood throughout the body, ensuring oxygenation of organs and tissues.
• This is achieved through rhythmic contractions occurring around 70 times per minute.
• Cardiac contractility relies on the synchronized contraction of cardiomyocytes (heart muscle cells).
• Cardiac contractility reflects the force generated by cardiomyocytes during contraction.
• Cardiomyocyte contraction is initiated by depolarization.
• Depolarization involves ion movement across the cell membrane, reducing its negative charge.
• Sufficient depolarization in one cell triggers calcium influx into neighboring cells, causing them to depolarize as well.
• A wave of depolarization spreads through the heart, dictating the heart rate.
• Depolarization waves originate in the sinoatrial (SA) node.
• If depolarization waves occur once per second, the heart beats 60 times per minute.
• Cardiomyocytes feature branches and intercalated disks with gap junctions for ion transfer between cells.
• Calcium ion movement through gap junctions stimulates depolarization in adjacent cells.
• Transverse tubules (T-tubules) are membrane invaginations that increase the cardiomyocyte's surface area.
• The sarcoplasmic reticulum stores intracellular calcium, which is critical for contraction.
• A few calcium ions flow through gap junctions when a depolarization wavefront reaches a cardiomyocyte.
• Sodium channels open if a threshold membrane potential is reached on the cell membrane.
• Depolarization prompts calcium and sodium ions to enter the cell.
• T-tubules facilitate calcium delivery deep into the cell.
• Intracellular calcium binds to ryanodine receptors on the sarcoplasmic reticulum, triggering further calcium release.
• This calcium-induced calcium release activates actin and myosin (myofilaments), which are contractile proteins.
• Myosin grabs and pulls on actin using ATP, creating cross-bridges and shortening the muscle fiber.
• Calcium ions are eventually removed by ion transporters, utilizing ATP or concentration gradients.
• Factors influencing cardiomyocyte contractility include intracellular calcium concentration.
• Higher intracellular calcium levels enhance cardiac contractility.
• Intracellular calcium concentrations rely on the total intracellular calcium, as well as the amount stored and released by the sarcoplasmic reticulum.
• The autonomic nervous system is a main method to control intracellular calcium.

Influence of the Autonomic Nervous System

• The heart receives innervation from both parasympathetic and sympathetic neurons.
• Sympathetic neurons exert a positive inotropic effect, increasing contractility.
• Sympathetic stimulation boosts contractility through the release of catecholamines like norepinephrine, which bind to beta 1 receptors on cardiomyocytes.
• Activation of beta 1 receptors leads to phosphorylation of proteins like sarcolemmal calcium channels, enhancing calcium release from the sarcoplasmic reticulum.
• Phosphorylation of phospholamban (on the sarcoplasmic reticulum membrane) activates calcium ATPase, a calcium pump that moves calcium from the cytoplasm back into the sarcoplasmic reticulum, increasing calcium storage.
• Phosphorylation of plasma membrane L-type calcium channels increases their permeability to calcium.
• Parasympathetic stimulation has a negative inotropic effect, decreasing contractility.
• Acetylcholine activates muscarinic M2 receptors on cardiomyocytes, inhibiting calcium channels.
• Reduced calcium channel activity results in decreased calcium influx and release from the sarcoplasmic reticulum.
• Parasympathetic stimulation also reduces heart rate by acting on the sinoatrial node.

Heart Rate

• Heart rate independently affects contractility.
• Increased heart rate leads to more action potentials and greater calcium influx per unit of time.
• The sarcoplasmic reticulum accumulates more calcium with higher heart rates.
• Increased heart rate due to sympathetic stimulation enhances calcium release, uptake, and storage in the sarcoplasmic reticulum through phosphorylation of phospholamban and sarcolemmal calcium channels.
• The positive staircase effect demonstrates a gradual increase in inotropy with increasing heart rate as calcium accumulates.
• Maximum inotropy is achieved when the sarcoplasmic reticulum reaches its maximum storage level.
• Postextrasystolic potentiation involves a premature heartbeat that is not commanded by the sinoatrial node.
• Premature beats have weaker contractions due to a transient refractory period of ryanodine receptors.
• Sarcoplasmic calcium load increases following a premature beat, resulting in a stronger contraction as all accumulated calcium releases together.

Glycosides

• Glycosides are drugs that can elevate intracellular calcium levels.
• Digoxin, a common glycoside, inhibits the sodium-potassium ATPase in the cardiomyocyte membrane and binds to the extracellular potassium binding site.
• Sodium-potassium ATPase normally pumps three sodium ions out and two potassium ions in, using one ATP.
• Inhibition of sodium-potassium ATPase reduces sodium expulsion, increasing intracellular sodium concentration and decreasing the sodium gradient.
• This reduced sodium gradient impairs the calcium-sodium exchanger, which normally pumps calcium out of the cell using the energy from sodium influx.
• Subsequently, less calcium is pumped out by the calcium-sodium exchanger, resulting in increased intracellular calcium and enhanced inotropy.
• Glycosides are primarily used for patients with congestive heart failure to improve ventricular contraction strength.

Learn about cardiac contractility, the force generated by cardiomyocytes during contraction. Understand how depolarization, initiated by ion movement, triggers calcium influx and spreads through the heart, dictating heart rate. Discover the role of the sinoatrial node and the significance of cardiomyocyte structure in ion transfer.