How is each cardiac cycle initiated (identify the specific cells and ion channel
ID: 63099 • Letter: H
Question
How is each cardiac cycle initiated (identify the specific cells and ion channels responsible for initiating the action potential in the normal human heart)? Once that action potential reaches the cardiac myocyte, how is that electrical signal converted into a mechanical response (include the molecular steps from action potential through crossbridge formation)? In your answer, address any differences in the cardiac excitation-contraction coupling (conversion of electrical to mechanical response) from skeletal muscle.
Explanation / Answer
Cardiac muscles are self-exciting and do not need nervous stimuli. Their rhythmic contractions are generated spontaneously, and are coordinated by sinoatrial (SA) and atrioventricular (AV) nodes. SA node is called pacemaker of heart. It generates electrical stimuli by creating an action potential.
At resting stage, cardiac myocytes have a negative membrane potential. K+ is the principal cation in the cell, Na+ and Cl- are main anions. Cardiac pacemaker cells are connected to adjoining cardiac myocytes through gap junctions. These gap junctions allow spontaneous depolarization of myocytes.
Resting membrane potential: This is due to the differences in ionic concentrations across the membrane and differences in conductance across the cell membrane, of different ions. Membrane are selectively permeable, especially to K+ ions and are relatively impermeable to other ions. Myocytes at pace maker undergo automatic depolarization, until they reach a potential around -40 mV. Depolarization occurs due to influx of Na+ ions through voltage-dependent channels. Sodium channels of cardiac pacemaker are unique in that they open when the voltage is more negative, immediately after the end of a previous action potential.
In cardiac myocytes, depolarization depends on activation of L-type calcium channels. The large influx of calcium ions generate action potentials. Further action potential is generated by activation and opening of fast Na+ channels. The large influx of calcium ions initiates contraction of the cells,.
During repolarization, the L-type calcium channels close, while the slow delayed rectifier K+ channels remain open. Thus, more potassium leak channels open and efflux of potassium from the cell to outside occurs. This generates a negative change in membrane potential, which further stimulate more K+ channels to open. The potassium channels close when the potential is restored to above -90 mV.
The wave of action potential from SA node is propagated to Purkinje fibers and makes them depolarized. The gap junctions allow the spontaneous depolarization transfer to action potential to contractile cells. The flow of positive ions through these gap junctions initiates small voltage change in contractile cells. The contractile cells start to depolarize by allowing influx of Na+ ions.
Excitation-contraction coupling: The process by which an electrical action potential is converted into mechanical energy. This is mediated by contractile proteins. Calcium is the modulator that couples electrical excitation to physical/mechanical contraction. The contractile proteins are myosin and actin, with the regulatory elements tropomyosin and troponin.
During repolarization of a cardiomyocyte, calcium enters the cell through L-type calcium channels. Increased calcium concentration activates ryanodine receptors on the sarcoplasmic reticulum. The receptors trigger further release of calcium from the SR to cytoplasm.
Calcium binds to troponin C, inhibiting troponin I.This brings conformation change in tropomyosin, and exposes active site between actin and myosin
Myosin heads interact with active sites on actin filaments, they stretch or flex.
Hydrolysis of ATP by ATPase on myosin induces cross-bridge formation between myosin head and active site of actin.
The number of cross bridges formed determines the strength of cardiac contraction
Interaction between myosin and actin triggers firing of myosin head, and causes it topull itself along the actin filament. This process is known as power stroke
Myosin head releases AADP, which bind to a new ATP and releases the actin filament
The cycle repeats allowing the myosin to travel along the actin moelcules and progressively shorten the muscle fibers. This occurs as long as the cytosolic calcium ion concentration remainspretty high to inhibit the action of troponin I, and there is enough ATP in the cell to drive cross bridge formation