Muscle contraction initiated

Calcium and Vascular Smooth Muscle Contraction. Calcium acts on a number of sites associated with the control of the cytoplasmic calcium concentration. Vascular smooth muscle contraction can be initiated by the opening of the slow calcium channel aUowing influx of extraceUular calcium through the sarcolemmal membrane into the cytoplasmic compartment. The iatraceUnlar calcium concentration increases to 1 x 10 Af, a threshold concentration necessary to initiate contraction. 

In the presence of calcium, the primary contractile protein, myosin, is phosphorylated by the myosin light-chain kinase initiating the subsequent actin-activation of the myosin adenosine triphosphate activity and resulting in muscle contraction. Removal of calcium inactivates the kinase and allows the myosin light chain to dephosphorylate myosin which results in muscle relaxation. Therefore the general biochemical mechanism for the muscle contractile process is dependent on the avaUabUity of a sufficient intraceUular calcium concentration. 

Another mechanism in initiating the contraction is agonist-induced contraction. It results from the hydrolysis of membrane phosphatidylinositol and the formation of inositol triphosphate (IP3)- IP3 in turn triggers the release of intracellular calcium from the sarcoplasmic reticulum and the influx of more extracellular calcium. The third mechanism in triggering the smooth muscle contraction is the increase of calcium influx through the receptor-operated channels. The increased cytosolic calcium enhances the binding to the protein, calmodulin [73298-54-1]. 

Neuromuscular junction (NMJ) is the synapse or junction of the axon terminal of motoneurons with the highly excitable region of the muscle fibre s plasma membrane. Neuronal signals pass through the NMJ via the neurotransmitter ACh. Consequent initiation of action potentials across the muscle s cell surface ultimately causes the muscle contraction. 

Muscle contraction is initiated by a signal from a motor nerve. This triggers an action potential, which is propagated along the muscle plasma membrane to the T-tubule system and the sarcotubular reticulum, where a sudden large electrically excited release of Ca " into the cytosol occurs. Accessory proteins closely associated with actin (troponins T, I, and C) together with tropomyosin mediate the Ca -dependent motor command within the sarcomere. Other accessory proteins (titin, nebulin, myomesin, etc.) serve to provide the myofibril with both stability... 

Smooth muscles, as the name implies, do not contain sarcomeres. In fact, it was initially difficult to demonstrate the presence of thick filaments in smooth muscle, although their presence is now well-established. On the other hand, it is very difficult to demonstrate thick filaments in highly motile cells, such as macrophages and neutrophils, and this may reflect the necessity to rapidly form and redistribute cytoskeletal elements during migration. Thick filaments in smooth muscles appear to be considerably longer than those in striated muscles. They run diagonally in smooth muscle cells and attach to the membrane at structures known as dense bodies. Thus, there is a cork-screw effect when smooth muscles contract (Warshaw etal., 1987). 

One should note overall, that while some of these suggested mechanisms may in the future prove to have a role in the control of smooth muscle contraction, in chemically skinned preparations maximum force development follows activation by the MLCK active subunit in extremely low Ca " ion concentrations. The conclusion can hardly be avoided that phosphorylation alone is sufficient for activation, and if another mechanism is involved, it is not necessary for the initial genesis of force. If such mechanisms are operative, then they might be expected to run in parallel or consequent to myosin phosphorylation. A possible example of this category of effect is that a GTP-dependent process (G-protein) shifts the force vs. Ca ion concentration relationship to lower Ca ion concentrations. This kind of mechanism calls attention to the divergence of signals along the intracellular control pathways. 

Voluntary muscle contraction is initiated in the brain-eliciting action potentials which are transmitted via motor nerves to the neuromuscular junction where acetylcholine is released causing a depolarization of the muscle cell membrane. An action potential is formed which is spread over the surface membrane and into the transverse (T) tubular system. The action potential in the T-tubular system triggers Ca " release from the sarcoplasmic reticulum (SR) into the myoplasm where Ca " binds to troponin C and activates actin. This results in crossbridge formation between actin and myosin and muscle contraction. 

Ca " plays a key role in the initiation of muscle contraction by binding to troponin C. In skeletal mus-... 

Tension-type headache (TTH) is the most common primary headache disorder. It is often underrepresented in clinical practice, as many patients do not present for care.6 The term tension-type headache is used to describe all headache syndromes in which muscle contraction is the most significant factor in the pathogenesis of pain. The 1-year prevalence of TTH in the population ranges from 30% to 90%.6 It is more common in adult females. Environmental factors, as opposed to genetic predisposition, play a more central role in their development. Tension-type headaches can be further divided into episodic or chronic the mean frequency of attacks is 3 days per month in episodic disorders, and chronic TTH is defined as 15 or more attacks in a 1-month period.7 The estimated prevalence of chronic TTH is less than 5%.6 Some researchers believe that chronic TTHs represent a continuum of headache severity with migraine headache.8 When severe headaches are difficult to differentiate clinically, treatment should initially target TTH. 

Psychogenic dysfunction occurs if a patient does not respond to psychic arousal. It occurs in up to 30% of all cases of ED. Common causes include performance anxiety, strained relationships, lack of sexual arousability, and overt psychiatric disorders such as depression and schizophrenia.5 It is postulated that the anxious or nervous man will have excessive stimulation of the sympathetic system, leading to smooth muscle contraction of arterioles and vascular spaces within erectile tissue.6 O Many patients may initially have organic dysfunction, but develop a psychogenic component as they try to cope with their inability to achieve an erection. It has been estimated that up to 80% of ED cases have an organic cause, with many having a psychogenic component as well.1... 

Altered release. Tetanus is an infectious disease caused by the bacterium Clostridium tetani. This bacterium produces a neurotoxin active on inhibitory synapses in the spinal cord. Motor neurons, which supply skeletal muscle and cause contraction, have cell bodies that lie in the spinal cord. Under normal circumstances, these motor neurons receive excitatory and inhibitory inputs from various sources. The balance of these inputs results in the appropriate degree of muscle tone or muscle contraction. Tetanus toxin prevents the release of gamma amino butyric acid (GABA), an important neurotransmitter active at these inhibitory synapses. Eliminating inhibitory inputs results in unchecked or unmodulated excitatory input to the motor neurons. The resulting uncontrolled muscle spasms initially occur in the muscles of the jaw, giving rise to the expression lockjaw. The muscle spasms eventually... 

Slow-wave potentials also involve gradual depolarization of the cell membrane, but these depolarizations do not necessarily reach threshold. Therefore, the depolarization may simply be followed by repolarization back to the initial membrane potential. These slow "wave-like" potentials occur rhythmically and do not lead to smooth muscle contraction. The peak-to-peak amplitude of the slow-wave potential is in the range of 15 to 30 mV. Therefore, under the appropriate conditions, the depolarization phase of the slow-wave potential may, in fact, reach threshold. When this occurs, a burst of action potentials is generated, resulting in muscle contraction. 

Arteriolar resistance changes that take place in order to maintain a constant blood flow are explained by the myogenic mechanism. According to this mechanism, vascular smooth muscle contracts in response to stretch. For example, consider a situation in which blood pressure is increased. The increase in pressure causes an initial increase in blood flow to the tissue. However, the increased blood flow is associated with increased stretch of the vessel wall, which leads to the opening of stretch-activated calcium channels in the vascular smooth muscle. The ensuing increase in intracellular calcium results in vasoconstriction and a decrease in blood flow to the tissue toward normal. 

Increases in the concentration of calcium in the cytosol provides a signal that can initiate muscle contraction, vision, and other signaling pathways. The response depends on the cell type. In muscle, a transient rise in the cytosolic calcium levels (from opening calcium channels in the sarcoplasmic reticulum) causes contraction. This signaling in contraction is a direct consequence of electrical activation of the voltage-gated channel. 

Smooth muscle is distributed throughout the body, largely around hollow structures such as blood vessels, the gastrointestinal tract and the genitourinary system. Normal function requires that the smooth muscles contract and relax at appropriate times, and abnormalities of contraction underlie such important pathologies as hypertension, incontinence and abnormal childbirth. Since contraction is initiated by an increase of cytoplasmic Ca2+ concentration then normal function requires appropriate Ca2+ handling. 

An initial hint that Ca2+ stores are present and functional in smooth muscle cells came from earlier experiments revealing that agonist-induced contractions could be observed in the absence of extracellular Ca2+. It is now known that smooth muscle Ca2+ stores express two types of Ca2+ release channels, the ryanodine receptor (RyR) and the inositol-1,4,5-trisphosphate (L1SP3) receptor (L1SP3R) (Somlyo Somlyo 1994). Recent studies have shown that Ca2+ release from intracellular Ca2+ stores plays various important roles in the regulation of smooth muscle contraction. Local and transient releases of Ca2+ from RyR near the surface membrane, which are called Ca2+ sparks, activate Ca2+-sensitive K+... 

Horikawa Y, Goel A, Somlyo AP, Somlyo AV 1998 Mitochondrial calcium in relaxed and tetanized myocardium. Biophys J 74 1579—1590 Horiuti K, Somlyo AV, Goldman YE, Somlyo AP 1989 Kinetics of contraction initiated by flash photolysis of caged adenosine triphosphate in tonic and phasic smooth muscles. J Gen Physiol 94 769-781... 

The discovery that ATP was not only the source of the energy required for muscle contraction but was apparently directly involved in the contractile process was an enormous stimulus to biochemists and muscle biologists. In the early 1950s attempts were made to determine if the ATP was hydrolyzed to initiate the contraction or was merely involved in the recovery process. Because of the speed with which contraction occurs, experiments had to be performed with amphibian... 

A means of co-ordinating muscle contraction with glycogenolysis is required. A dramatic 100-fold increase in cytosolic Ca2+ concentration from 10 7 to 10 5 molar initiates both glycogenolysis and muscle contraction. This increase in cytosolic calcium concentration is mainly due to release of calcium from the sarcoplasmic reticulum in response to acetylcholine stimulation of the muscle fibre (Figure 7.7). 

Muscle spindles are composed of nuclear bag (dynamic) and chain (static) fibres known as intrafusal fibres and these are innervated by y motor neurones. Extrafusal fibres make up the muscle bulk and are innervated by a motor neurones. Stimulation of the muscle spindle leads to increased skeletal muscle contraction, which opposes the initial stretch and maintains the length of the fibre. This feedback loop oscillates at 10 Hz, which is the frequency of a physiological tremor. 

Within 30 minutes of their administration, 6 -adrenergic drugs often reverse most of the functional deficit in Monday morning byssinotics. As there is no mucous secretion, airway smooth muscle contraction is considered the primary response. Exposure of man to histamine aerosols produces pulmonary function changes similar to those seen after exposure to dust extract. However, exposure to histamine aerosol invariably initiates constriction of smooth muscle more rapidly than exposure to cotton dust ( <15 minutes), and dissipates within minutes, while the acute effects of inhalation of cotton dust and dust extracts lasts for hours. The slowly developing and prolonged effects of dust and extracts suggest that mediators other than histamine are involved. 

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