Ion Channel Function In Endothelial Regulation Of The Coronary Circulation
Endothelin is a major endothelium-derived contracting factor and ion channels in smooth muscle contribute to endothelin-induced constriction of the coronary circulation . Signaling centers around L-type Ca2+ channel activity and there are two general mechanisms of regulation: transmembrane signaling that directly activates L-type Ca2+ channels and membrane depolarization caused by activation of nonselective cation and Cl channels or inhibition of K+ channels. Endothelin activates L-type Ca2+ currents in coronary myocytes , an effect that can also be observed at the single-channel level . In the cell-attached single channel experiments, the L-type Ca2+ channels under study were physically isolated from the bath by the patch pipette therefore, these experiments demonstrate that diffusible intracellular signaling entities were responsible for activation. Nonselective cation channels can depolarize the membrane and also serve as a Ca2+ entry pathway, as TRPC channels are activated by endothelin in coronary smooth muscle . Similarly, endothelin depolarizes coronary smooth muscle membrane potential by stimulating a Ca2+-activated Cl current and inhibiting BKCa, KATP, and Kir channels .
Basic Anatomy: The Heart Is A Four Chambered Pump
The primary function of the heart is to transfer sufficient blood from the venous system to the arterial side of the circulation under sufficient pressure to maintain the circulatory needs of the body. As illustrated in Figure 2, the heart consists of four chambers which act as two separate pump systems. The right atrium & ventricle pump deoxygenated blood collected from the great veins into the pulmonary circulation, via the pulmonary artery. The left atrium & ventricle pump oxygenated blood received from the pulmonary system into the systemic circulation. The atria, which sit dorsal to the ventricles are relatively thin walled, and their primary functions are to serve as a blood reservoir, and to assist in filling the ventricles with blood. In this sense they serve as primer pumps. The ventricular chambers have much thicker walls . They can be thought of as the power pumps of the heart since they provide the primary force for pumping blood into the pulmonary and systemic circulations. The pattern with which the heart contracts and relaxes is cyclical, and is divided into a period of relaxation , and a period of contraction .
Ion Channels Myogenic Responses And Coronary Autoregulation
Stretch-activated nonselective cation current in coronary vascular smooth muscle: effects on the intracellular Ca2+ concentration. Panel A contains a photomicrograph of representative porcine coronary smooth muscle cells. A patch clamp pipette is used to hold one end of a cell and record electrical activity while longitudinal stretch is applied with a second pipette and piezoelectric translator panel B shows that the magnitude of depolarizing inward current is related to the degree of longitudinal stretch in a porcine coronary smooth muscle cell . Panel C demonstrates that, in porcine coronary myocytes, stretch-induced increases in intracellular Ca2+ ultimately depend upon extracellular Ca2+. Arrows indicate the initiation of longitudinal stretch. In the presence of extracellular Ca2+, stretch-induced increases in intracellular Ca2+ were rapid and repeatable. In the absence of extracellular Ca2+, longitudinal stretch still elicited Ca2+ transients, but internal stores were quickly depleted .
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When Heart Rate Or Rhythm Changes Are Minor
Many changes in heart rate or rhythm are minor and do not require medical treatment if you do not have other symptoms or a history of heart disease. Smoking, drinking alcohol or caffeine, or taking other stimulants such as diet pills or cough and cold medicines may cause your heart to beat faster or skip a beat. Your heart rate or rhythm can change when you are under stress or having pain. Your heart may beat faster when you have an illness or a fever. Hard physical exercise usually increases your heart rate, which can sometimes cause changes in your heart rhythm.
Natural health products, such as goldenseal, oleander, motherwort, or ephedra , may cause irregular heartbeats.
It is not uncommon for pregnant women to have minor heart rate or rhythm changes. These changes usually are not a cause for concern for women who do not have a history of heart disease.
Well-trained athletes usually have slow heart rates with occasional pauses in the normal rhythm. Evaluation is usually not needed unless other symptoms are present, such as light-headedness or fainting , or there is a family history of heart problems.
Neuronal Control Of The Heart
The rate and force with which the heart contracts is modulated by both the sympathetic and parasympathetic branches of the autonomic nervous system . The degree of basal tone on the heart is predominantly vagal when the body is at rest. In normal adults, the average resting heart rate at rest is ~70 beats/minute, but can increase to rates considerably above 100 during exercise or emotional excitement , and may decrease by 10 to 20 beats/minute during sleep. Sympathetic nerves innervate both the atria and ventricles , while vagal nerves innervate only the atria, SA node, AV node and Purkinje fiber system.
Stimulation of sympathetic nerves increases heart rate, conduction velocity thru the AV node and the force of ventricular contraction. In contrast, stimulation of vagal nerves reduces heart rate and conduction velocity through the AV node, but does little to ventricular contractility.
Lagniappe Sidebar On Inward Rectification
The channel that produces IK1 is frequently referred to as an inward rectifier. Inward rectification describes the behavior of the channel to pass current most easily in the inward direction vs. the outward direction , similar to an electrical diode. Inward rectification can be caused by substances in the cytoplasm or associated with the internal surface of the cell membrane that get swept into the channel whenever the direction of the current becomes strongly outward i.e. whenever the voltage becomes positive to EK. This allows a channel with otherwise little voltage dependence to shut off at voltages positive to EK. The biological advantage of reducing the amplitude of this current at voltages positive to EK is that it allows other currents to determine the shape of the cardiac action potential without having to dominate an otherwise massively large outward current, and conserve the energy that would be needed to pump all the K ions that would otherwise be lost back into the cell. Having a longer action potential duration with a plateau phase is also important for excitation-contraction coupling which is regulated by calcium influx during phase 2.
This Video Relates The Cardiac Cycle To The Ecg:
Blood flow through the capillary beds is regulated depending on the bodyâs needs and is directed by nerve and hormone signals. For example, after a large meal, most of the blood is diverted to the stomach by vasodilation of vessels of the digestive system and vasoconstriction of other vessels. During exercise, blood is diverted to the skeletal muscles through vasodilation while blood to the digestive system would be lessened through vasoconstriction. The blood entering some capillary beds is controlled by small muscles, called precapillary sphincters. If the sphincters are open, the blood will flow into the associated branches of the capillary blood. If all of the sphincters are closed, then the blood will flow directly from the arteriole to the venule through the thoroughfare channel. These muscles allow precise control when capillary beds receive blood flow. At any given moment only about 5-10% of our capillary beds actually have blood flowing through them.
Precapillary sphincters are rings of smooth muscle that regulate the flow of blood through capillaries they help control the location of blood flow to where it is needed. Valves in the veins prevent blood from moving backward.
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Does An Ecg Provides Direct Information About Valve Function
4.9/5canvalveECG provides direct information about valve function
Furthermore, what would happen to the SA node if a chemical blocker was used to reduce transport of Na+ into the pacemaker cells? The SA node would depolarize more slowly, reducing the heart rate. Diffusion of Na+ into the pacemaker cell causes a gradual depolarization of the cell membrane, called the pacemaker potential.
Similarly one may ask, when an ectopic pacemaker leads to an Extrasystole the?
A& P Ch17
|front 117 When an ectopic pacemaker leads to an extrasystole, the ______.||back 117 ventricles contract before the atria contract|
|front 119 Heart murmurs caused by a stenotic mitral valve ______.||back 119 are detected while blood flow into the left ventricle is reduced|
Which is most responsible for the synchronized contraction of cardiac muscle tissue?
In cardiac muscle, intercalated discs connecting cardiomyocytes to the syncytium, a multinucleated muscle cell, to support the rapid spread of action potentials and the synchronized contraction of the myocardium.
Conduction System Of The Heart
If embryonic heart cells are separated into a Petri dish and kept alive, each is capable of generating its own electrical impulse followed by contraction. When two independently beating embryonic cardiac muscle cells are placed together, the cell with the higher inherent rate sets the pace, and the impulse spreads from the faster to the slower cell to trigger a contraction. As more cells are joined together, the fastest cell continues to assume control of the rate. A fully developed adult heart maintains the capability of generating its own electrical impulse, triggered by the fastest cells, as part of the cardiac conduction system. The components of the cardiac conduction system include the sinoatrial node, the atrioventricular node, the atrioventricular bundle, the atrioventricular bundle branches, and the Purkinje cells ).
Normal cardiac rhythm is established by the sinoatrial node, a specialized clump of myocardial conducting cells located in the superior and posterior walls of the right atrium in close proximity to the orifice of the superior vena cava. The SA node has the highest inherent rate of depolarization and is known as the pacemaker of the heart. It initiates the sinus rhythm, or normal electrical pattern followed by contraction of the heart.
Atrioventricular Bundle , Bundle Branches, and Purkinje Fibers
Membrane Potentials and Ion Movement in Cardiac Conductive Cells
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Multiple Ionic Currents Underlie The 5 Phases Of The Cardiac Action Potential
The cardiac action potential gains its peculiar shape from the opening and closing of different voltage sensitive channels. The flux of ions through each channel drives the membrane potential toward the equilibrium potential for that species of ion. For example, when cardiac cells are left unstimulated , the only channel type that opens on a regular basis is an inwardly rectifying K-selective channel which produces a K current called IK1 .
The selective permeability of the resting membrane to K ions causes the potential difference across the resting cell membrane to approach the equilibrium potential for K ions . In contrast, when heart cells are partially depolarized by an invading action potential, these K channels close, and a large number of excitable Na channels transiently open. This drives the membrane potential towards the equilibrium potential for Na ions , and produces the action potential upstroke . Almost all Na channels become rapidly inactivated within ~1 msec at normal body temperature. However, a small fraction of Na channels do not fully inactivate, and contribute to maintenance of the plateau phase of the ventricular action potential. This non-inactivating component can be blocked by Na channel blocking drugs .
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Ans Modulation Of Automaticity
Neurotransmitters such as acetylcholine and norepinephrine alter automaticity by modulating ion channel behavior, which in turn alters the steepness of the slope of diastolic depolarization.
Vagal stimulation increases the magnitude of the ligand-gated K current , an effect mediated by muscarinic m2 receptors . A greater efflux of K ions results in a less steep slope of phase 4 depolarization in both the SAN and in Purkinje fibers . This is the mechanism by which vagal stimulation reduces the heart rate when the body is at rest . Very intense vagal stimulation can also reduce automaticity by hyperpolarizing the maximum diastolic potential . .
Sympathetic stimulation increases the magnitude of both the L-type Ca current, and If. A greater influx of Ca and Na ions results in a steeper slope of phase 4 depolarization, and an increase in heart rate during exercise and fight-or-flight situations.
Note that drugs that directly or indirectly affect If will influence Purkinje fiber automaticity, but an L-type Ca channel blocker will not.
Figure 17. Effect of vagal stimulation and sympathetic stimulation on Purkinje fiber automaticity. Left: Vagal stimulation increases IKACh, resulting in an increase in K efflux that balances Na influx mediated by If, which eliminates automaticity. Right: Sympathetic stimulation increases If by
Integrative Control Of The Coronary Circulation
Left: Relationship between coronary venous PO2 and myocardial oxygen consumption at rest and during exercise before and during triple blockade of KATP channels, nitric oxide synthase and adenosine receptors . Right: Relationship between coronary venous PO2 and myocardial oxygen consumption at rest and during exercise before and during inhibition of adenosine receptors , KATP channels and/or nitric oxide synthase .
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What Is Diastolic Blood Pressure
The heart rests between beats so it can refill with blood. Doctors call this pause between beats “diastole.” Your diastolic blood pressure is the measurement during this pause before the next heartbeat.
A normal diastolic blood pressure during quiet rest is 80 mmHg or a little below. If you have high blood pressure, the diastolic number is often higher even during quiet rest.
Low diastolic pressure may be seen with dehydration or with severe bleeding. It also may happen if the arteries relax and widen.
Balance Between Coronary Blood Flow And Myocardial Metabolism
Relationship between coronary blood flow and coronary venous PO2 versus myocardial oxygen consumption in conscious instrumented swine at rest and during exercise under control conditions, following inhibition of pathway that produces similar reductions in coronary flow and myocardial oxygen consumption , and during a condition that produces progressive limitation in coronary vasodilation with increases in oxygen consumption . The physiologic limit of these relationships are depicted by the red line which represents the condition in which all oxygen delivered in extracted and consumed .
Left: Relationship between coronary blood flow and coronary venous PO2 in the right and left ventricle at rest and during exercise in dogs . Right: Relationship between coronary blood flow and coronary venous PO2 in response to exercise in swine and isovolemic hemodilution-induced anemia .
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The Normal Sinus Rhythm
The coordinated and synchronized contraction of the muscle cells in each chamber of the heart that occurs during each cardiac cycle of systole and diastole is achieved by a regular pattern of excitation that precedes each contraction. The time intervals that the cardiac impulse reaches each region of the heart during each beat of the cardiac cycle is illustrated in Figure 3.
The normal pattern of excitation begins with the spontaneous appearance of action potentials in the Sinoatrial node , which spontaneously generates action potentials at a frequency of 60-100 per minute. These action potentials spread rapidly through the left and right atria, and into the upper region of the atrioventricular node . Conduction through the AVN is slow, requiring more than a hundred milliseconds. This delay provides enough time for the atria to contract and assist in filling the ventricles with blood before they are stimulated to contract.
Figure 3. The pattern of transmission of the cardiac impulse through the heart during normal sinus rhythm. Reproduced from the wikipedia commons.
Structure Of Cardiac Muscle
Compared to the giant cylinders of skeletal muscle, cardiac muscle cells, or cardiomyocytes, are considerably shorter with much smaller diameters. Cardiac muscle also demonstrates striations, the alternating pattern of dark A bands and light I bands attributed to the precise arrangement of the myofilaments and fibrils that are organized in sarcomeres along the length of the cell a). These contractile elements are virtually identical to skeletal muscle. T tubules penetrate from the surface plasma membrane, the sarcolemma, to the interior of the cell, allowing the electrical impulse to reach the interior. The T tubules are only found at the Z discs, whereas in skeletal muscle, they are found at the junction of the A and I bands. Therefore, there are one-half as many T tubules in cardiac muscle as in skeletal muscle. In addition, the sarcoplasmic reticulum stores few calcium ions, so most of the calcium ions must come from outside the cells. The result is a slower onset of contraction. Mitochondria are plentiful, providing energy for the contractions of the heart. Typically, cardiomyocytes have a single, central nucleus, but two or more nuclei may be found in some cells.
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Innervation And Functional Receptor Distribution
Representative drawing of innervation of a coronary artery from Woollard .
Coronary blood flow responses to muscarinic receptor activation, either via the administration of acetylcholine or vagal stimulation, are highly species and concentration dependent with experiments in most animal models and healthy human vessels demonstrating significant endothelial-dependent vasodilation in vessels ranging between 50 and 400 m in diameter . Interestingly, acetylcholine administration has also been shown to produce vasoconstriction in human atrial arterioles, but dilation of human ventricular arterioles . Studies in swine, calves, and humans with atherosclerosis report vasoconstriction, likely because of the lack of muscarinic receptor expression . Muscarinic coronary vasodilation has been attributed to both M1 and M2 receptors, with stimulation of M2 receptors resulting in the redistribution of blood flow toward the subendocardium .
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