Cardiac muscle, contraction

Phosphodiesterase Inhibitors. Because of the complexity of the biochemical processes involved in cardiac muscle contraction, investigators have looked at these pathways for other means of dmg intervention for CHF. One of the areas of investigation involves increased cycHc adenosine monophosphate [60-92-4] (cAMP) through inhibition of phosphodiesterase [9025-82-5] (PDE). This class of compounds includes amrinone, considered beneficial for CHF because of positive inotropic and vasodilator activity. The mechanism of inotropic action involves the inhibition of PDE, which in turn inhibits the intracellular hydrolysis of cAMP (130). In cascade fashion, cAMP-catalyzed phosphorylation of sarcolemmal calcium-channels follows, activating the calcium pump (131). A series of synthetic moieties including the bipyridines, amrinone and milrinone, piroximone and enoximone, [77671-31-9], C22H22N2O2S, all of which have been shown to improve cardiac contractiUty in short-term studies, were developed (132,133). These dmgs... 

Dihydropyridine receptor (DHPR) is a member of voltage-dqiendent Ca2+ channels (CaVi, L-type), which specifically binds to dihydropyridine derivatives, a group of the Ca2+ channel blockers. Cav 1.1 works as the voltage sensor for skeletal muscle contraction, and Cay 1.2, as Ca2+-influx channel for cardiac muscle contraction. 

The Cellular and Molecular Basis of Skeletal and Cardiac Muscle Contraction... 

Ca normally circulates in the bloodstream, within a 2.25-2.50 mmol concentration range, bound to proteins (40 5%), complexed with ions (8-10%), and ionized as Ca " " (45-50%) (Weaver and Heaney, 2006a). Circulating Ca in excess of that required for maintenance of plasma levels is ideally transferred from the blood to be deposited in bone via the bone formation process. The Ca concentration outside of blood vessels in the ECF that bathes cells is tightly regulated close to 1.25 mmol (Weaver and Heaney, 2006a), almost to the point of invariance. It is this ECF Ca pool that cells are immediately reliant upon to sustain vital cellular functions that are imminently critical to the maintenance of life (e.g., cardiac muscle contraction). Circulating Ca is constantly utilized to replenish ECF pools, and when Ca derived from dietary intake is insufficient to replace the amoimt of Ca used for replenishment, Ca in bone is transferred to the blood via a bone resorption process. 

Ugur, M., and Turan, B. 2001. Adenosine triphosphate alters the selenite-induced contracture and negative inotropic effect on cardiac muscle contractions. Biol. Trace Elem. Res. 79 235-245. 

The synthesis of this tritium-labelled dihydropyridine derivative, 137, a powerful antihypertensive agent attenuating smooth muscle and cardiac muscle contractions by blocking the influx of calcium ions into vascular smooth muscle cells143, has been carried out144 by preparing initially the 3-nitrobenzaldehyde[4,6-3H] 138 of high specific activity in the four steps shown in equation 58. It was then used in the Hantzsch... 

Q5 Jo s tachycardia is due to the activation of the sympathetic nervous system to prepare the body for fight or flight . Stimulation of sympathetic nerves supplying the heart releases noradrenaline, which increases both the rate and force of cardiac muscle contraction via beta-1-receptor (/31-receptor) activation. 

Cardiac muscle cells are surrounded by an endomysi-um like the skeletal muscle cells. But innervation of autonomic nerves to the heart do not form any special junction like that found in skeletal muscle. Instead, the branching structure and extensive interconnectedness of cardiac muscle fibers allows for stimulation of the heart to spread into neighboring myocardial cells this does not require the individual fibers to be stimulated. Although external nervous stimuli can enhance or diminish cardiac muscle contraction, heart muscles can also contract spontaneously making them myogenic. Like skeletal muscle cells, cardiac muscle fibers can increase in size with physical conditioning, but they rarely increase in number. 

Cardiac muscle contraction is an electrical event initiated at the sinoatrial node. Each cardiac muscle cell fires an action potential as a result of excitation propagated from the sinoatrial node, which produces muscle cell contraction. A wave of action potentials spreads across the organ to produce coordinated contraction of the heart and efficient ejection of blood to the body. Excitation and the subsequent return of a cardiac muscle cell to rest (repolarization) during the action potential is dictated by the flow of ions across the cell membrane. Membrane repolarization is produced by the flow of potassium ions through various types of potassium channels. 

The noncarbohydrate moiety of a glycoside is known as the aglycone. Methanol, glycerol, sterols, and phenols may serve as aglycones. Glycosides, which stimulate cardiac muscle contractions and are used therapeutically. 

Mammals have four types of cells specialized for contraction skeletal muscle, cardiac muscle, smooth muscle, and myoepithelial cells (Table 21-2). Skeletal and cardiac muscles contract with more force and much more... 

Troponin complex is a heteromeric protein which plays an important role in the regulation of skeletal and cardiac muscle contraction. It consists of three subunits, troponin I (Tnl), troponin T (TnT), and troponin C (TnC). Each subunit is responsible for part of troponin complex function. For more than a decade, the cardiac form of Tn I (cTn I) has been known as a reliable marker of cardiac tissue injury. The greatest advantage of detection of cTn I is its cardio-specificity [31]. 

Its cellular functions comprise skeletal and cardiac muscle contraction cellular secretion exocrine, endocrine, and neurotransmitters, neural excitation and regulation of membrane ion transport enzyme regulation (gluconeogenesis and glycogenolysis) and cell growth and division. 

Stimulation of muscarinic receptors in the heart results in bradycardia, due to a slowing of conduction through the AV node, a decrease in firing of the SA node, and decreased force of cardiac muscle contraction. Muscarinic stimulation increases bladder tone, and muscarinic effects on smooth muscle may produce bronchoconstriction (particularly in patients with pulmonary disease), vasodilatation, increased exocrine secretions, and increased peristalsis. In the CNS, muscarinic receptor stimulation is involved in cognizance and motor function. 

Troponin is a heterotrimeric protein involved in the regulation of striated and cardiac muscle contraction. Most troponin in the cell is bound to the actin-tropomyosin complex in the muscle fibril. The three subunits of troponin consist of troponin-C, troponin-T, and troponin-l, each with a specific function in the regulatory process. Troponin-T and troponin-l exist as different isoforms in cardiac and skeletal muscle (sequences with a different amino acid composition), thus allowing the development of specific antibodies against each form. As a consequence, either cardiac troponin-T or cardiac troponin-l may be rapidly measured in blood samples by immunoassay with a good degree of specificity. 

The mechanism of cardiac contraction involves a G-protein signal transduction pathway, which regulates intracellular calcium concentrations. Activation of the Gs-protein involves the formation of intracellular cAMP, which thereby increases intracellular calcium, stimulating cardiac muscle contraction (see Chapter 4). Relaxation occurs when the released cAMP is hydrolyzed by cytosolic cAMP-dependent PDE3, one of the phosphodiesterase isofoms. Therefore, inhibition of PDE3 increases intracellular cAMP, promoting cardiac muscle contraction but vasodilation of vascular smooth muscle. (See Chapter 17 for more information about phosphodiesterases.)... 

A positive inotropic action that increases cardiac muscle contraction. 

Glycosides are known as digitalis glycosides. They inhibit the sodium-potassium pump and increase intracellular calcium. As a result, there is an increase in cardiac muscle contraction, decrease in the heart rate, and a decrease in conduction of electrical stimulus to the heart. 

PaUadino, J.L. 1990. Models of Cardiac Muscle Contraction and Relaxation. Ph.D. dissertation, University of Pennsylvania, Philadelphia. Univ. Microforms, Ann Arbor, Ml. 

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