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Shepherd cheap sildalis 120mg mastercard, GM and Erulkar generic sildalis 120 mg visa, SD (1997) Centenary of the synapses from Sherrington to the molecular biology of the synapse and beyond. Edited by Roy Webster Copyright & 2001 John Wiley & Sons Ltd ISBN: Hardback 0-471-97819-1 Paperback 0-471-98586-4 Electronic 0-470-84657-7 2 Control of euronal ctivity D. They do this using a combination of electrical signals (action potentials) and chemical signals (transmission). However, even the chemical signal has to be transduced to an electrical signal (the synaptic potential) in order to continue the process of communication from one neuron to another. Information is then coded in the frequency and pattern of action potential discharges. This chapter considers the question of how these electrical signals are generated and how their frequency and discharge patterns can be regulated. THE RESTING STATE: ION GRADIENTS, PUMPS AND POTENTIALS The electrical signals are carried by the movement of charged ions across the cell membrane. This makes use of the potential energy stored across the cell membrane in the form of ionic gradients. Concentration gradients for the principal ions across a typical nerve cell membrane are indicated in Fig. The cell interior has a high concentration of K‡ ions and a low concentration of Na‡,Cl7 and Ca2‡ ions relative to the exterior. Thus, the Na‡/K‡ exchange pump (Na‡/K‡ ATPase) in the outer membrane generates the primary Na‡ and K‡ gradients across the cell membrane. Other pumps (a Ca2‡ ATPase and/or a Na‡/Ca2‡ exchange pump) generate a high concentration gradient for Ca2‡ ions. It has been estimated that about 40% of the oxygen consumption of the brain is used to drive the Na‡/K‡ exchange pump. At rest, the normal value of this potential (Erest) in most nerve cells is around À70 mV (inside 7ve). In general, the ion pumps themselves are not directly responsible for this (though they can contribute, since they are not electroneutral). Instead, it is due primarily to the passive diffusion of K‡ ions back out of the cell down the chemical concentration gradient previously set up by the Na‡/K‡ exchange pump, leaving a small ‡ve charge deficit on the inside of the membrane. However, if K‡ were the only ion involved, then, from the K‡ concen- tration gradient, the Nernst equation predicts that the membrane potential should be about À90 mV: Neurotransmitters, Drugs and Brain Function. Webster &2001 John Wiley & Sons Ltd 34 NEUROTRANSMITTERS, DRUGS AND BRAIN FUNCTION Figure 2. Arrows show the direction of the electrochemical gradients for passive ionic movement. The 20 mV difference between E and E is usually rest K explained by assuming that the membrane is also slightly permeant to some other ion with a more positive equilibrium potential, such as Na‡. The membrane potential is then given by the Goldman±Hodgkin±Katz (GHK) or constant-field equation: ‡ ‡ ‡ ‡ E ˆ RT=zF lnf ‰K Šout ‡ a‰Na Šout†= ‰K Šin ‡ a‰Na Šin†g where a is the ratio of the permeability of Na‡ ions to that of K‡ ions (P =P ). The Na K GHK equation then predicts a value of À70 mV for Erest if the permeability of the membrane to Na‡ ions is about 4% of that to K‡ ions (P =P ˆ 0:04). However, it Na K CONTROL OFNEURONAL ACTIVITY 35 should be noted that, at this potential, although the fluxes of total cations in and out of the cell are equal, the cell will gradually accumulate Na‡ and lose K‡, which will have to be corrected by the Na/K exchange pump; since this involves energy expenditure, it is not a true equilibrium state. The GHK equation can be expanded to include terms for other ions, such as Cl7 ions, which can have a profound effect on the membrane potential under certain circumstances (e. Passive diffusion occurs entirely through ion channels Ð pore-forming membrane proteins. The resting potential may then be generated either by two sets of channels, one set permeant to K‡ and the other to Na‡ (or some other ion with a more positive equilibrium potential), with the former in the majority or opening more often; or a set of channels primarily permeant to K‡ but with some weak permeability to Na‡. Another class of K‡ channels that can contribute to the resting potential of neurons are inwardly- rectifying K‡ channels (Kir channels) Ð so-called because they conduct K‡ ions more readily into the cell than outwards. Both TASK and Kir can be inhibited by certain neurotransmitters which act on receptors that couple to phospholipase C-activating G-proteins, such as acetylcholine, substance P and TRH. As a result, these transmitters can induce a sustained depolarisation of the receptive neurons (e. Several transmitters, acting on receptors coupled to other G-proteins of the Gi/Go family, are capable of activating another class of Kir channels (G-protein-gated inward rectifiers or GIRK channels, also known as Kir3), thereby hyperpolarising the neuron (and inhibiting it). Other ion channels are closed at rest, but may be opened by a change in membrane potential, by intracellular messengers such as Ca2‡ ions, or by neurotransmitters. These are responsible for the active signalling properties of nerve cells and are discussed below (see Hille 1992, for a comprehensive account). This chapter concerns function, rather than structure, and hence does not systematically follow the structural classification. It is a transient electrical signal generated by the opening of voltage-gated Na‡ channels.

Which of the following represents the location of the cell lowing most specifically describes this condition? The examination reveals a hemiplegia involving the left upper and lower extremities buy sildalis 120 mg fast delivery, sensory losses (pain purchase 120mg sildalis, thermal sensations, and proprioception) on the left side of the body and 286 Q & A’s: A Sampling of Study and Review Questions with Explained Answers face, and a visual deficit in both eyes. MRI shows an area of infarction Answers for Chapter 7 consistent with the territory served by the anterior choroidal artery. The (B) Left nasal hemianopsia motor loss is ipsilateral to the damage and the sensory loss is con- (C) Left superior quadrantanopia tralateral; second order fibers conveying pain information cross in (D) Right homonymous hemianopsia the anterior white commissure ascending one to two spinal seg- (E) Right superior quadrantanopia ments in the process. In this patient, the lesion is on the left side at about the T6 level; this explains the loss of pain sensation on the 81. Which of the following most specifically identifies the pattern of right beginning at the T8 dermatome level. The weakness of the extremities in this woman is most likely due tremities. An alternating hemiplegia is the combination of a mo- to damage to which of the following? Answer C: While the causes of swallowing difficulties may be (E) Thalamocortical fibers to sensory cortex on the right central or peripheral (and multiple), this particular problem is called dysphagia. A 16-year-old boy is brought to the family physician by his or power of a movement and is commonly seen in cerebellar dis- mother. Dysarthria is difficulty in speaking, and dyspnea is a difficulty school even though he is a hard worker and is well behaved. The in breathing; the latter is usually associated with diseases of the examination reveals that the boy has a sensorineural hearing loss lungs or heart. Which of the following alternating movements, is seen most commonly in cerebellar dis- represents the most likely location of the lesion in this boy? Answer E: One possible cause of trigeminal neuralgia (tic (B) Cochlea douloureux) is compression of the trigeminal root by the superior (C) External ear cerebellar artery or its main branches; surgical relocation of the (D) Inferior colliculus aberrant vessel (neurovascular decompression) relieves the symp- (E) Middle ear toms. Hemifacial spasm may be caused by compression of the fa- cial nerve by the anterior inferior cerebellar artery (commonly 84. Which of the following laminae of the lateral geniculate nucleus called AICA). The other choices do not cause trigeminal neuralgia receive input from the contralateral retina? Answer E: The rostral interstitial nucleus of the medial longitu- (D) 2, 3, 5 dinal fasciculus receives cortical input from the frontal eye field on (E) 3, 4, 5, 6 the ipsilateral side and projects to the ipsilateral (heavy) and con- tralateral (light) oculomotor and trochlear nuclei. A 12-year-old girl is brought to the pediatrician by her mother regarded as the vertical gaze center. The paramedian pontine who explains that the girl has started to “act funny”. The oculomotor reveals that the girl was treated for a hemolytic streptococcus in- and abducens nuclei do not receive direct input from the frontal fection 4 weeks before the appearance of her symptoms; the eye field and the Edinger-Westphal is a visceromotor nucleus con- mother states that the girl has had this problem for 3 weeks. Answer C: The absence of, or the aberrant development of, This girl is most likely suffering from which of the following? Mesoderm of the (E) Weber syndrome head outside of the pharyngeal arches gives rise to the extraocular muscles and muscles of the tongue. The muscles of mastication Q & A’s: A Sampling of Study and Review Questions with Explained Answers 287 (plus the tensor tympani, tensor veli palati, mylohyoid, anterior ing of written or printed words. Aphonia is a loss of the voice fre- belly of the digastric) arise from arch 1, the stylopharyngeus from quently due to disease of, or injury to, the larynx. Aphasia is seen arch 3, and striated muscles of the pharynx, larynx, and upper in individuals with a lesion in the dominant hemisphere, and is esophagus from arch 4. Answer C: Hypothalamocerebellar fibers that project to the cerebellar nuclei and cortex contain histamine. Answer C: The Korsakoff syndrome is a constellation of deficits several neurons that are located in the cerebellar cortex, and in the include memory loss, confabulation, amnesia, and dementia Purkinje cells glutamate is found in many pontocerebellar fibers that is seen in chronic alcoholics; the manifestations are related, in and in granule cells of the cerebellar cortex; and noradrenalin is part, to excessive alcohol consumption and malnutrition. Serotonin is found in cells of the peutic doses of thiamine are used to treat this disease. Broca apha- reticular formation and in some raphe cells that project to the sia (nonfluent or expressive aphasia) results from lesions in the cerebellum. The Klüver-Bucy syndrome is related to bilateral lesions to the amygdaloid complex, and Pick disease is de- 8. Answer C: The best localizing sign in this patient is the paucity mentia related to atrophy of the frontal and temporal lobes. Mun- of eye movement and dilated pupil on the left; this indicates a le- chausen syndrome is the fabrication or feigning of illness or disease sion of the midbrain on the left at the level of the exiting oculo- to gain attention or control.

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However 120mg sildalis for sale, the extraction of The inverse relationship between GFR and plasma [cre- PAH by healthy kidneys at suitably low plasma PAH con- atinine] allows the use of plasma [creatinine] as an index of centrations is not 100% but averages about 91% cheap sildalis 120mg line. Assuming GFR, provided certain cautions are kept in mind: 100% extraction underestimates the true renal plasma flow by 1) It takes a certain amount of time for changes in GFR about 10%. To calculate the true renal plasma flow or blood to produce detectable changes in plasma [creatinine]. A young, muscular man will have a higher plasma [creatinine] than an older woman with reduced muscle Net Tubular Reabsorption or Secretion of a mass. Substance Can Be Calculated From Filtered 3) Some drugs inhibit tubular secretion of creatinine, leading to a raised plasma [creatinine] even though GFR and Excreted Amounts may be unchanged. The rate at which the kidney tubules reabsorb a substance The relationship between plasma [creatinine] and GFR can be calculated if we know how much is filtered and how is one example of how a substance’s plasma concentration much is excreted per unit time. The same relationship is observed for stance exceeds the rate of excretion, the kidney tubules several other substances whose excretion depends on GFR. The equation is: For example, when GFR falls, the plasma [urea] (or blood T P GFR U V˙ (8) urea nitrogen, BUN) rises in a similar fashion. In equations 8 and 9, we assume that substance X is RBF RPF/(1 Hematocrit) (4) freely filterable. If, however, substance X is bound to the The hematocrit is easily determined by centrifuging a plasma proteins, which are not filtered, then it is necessary blood sample. Renal plasma flow is estimated by measuring to correct the filtered load for this binding. For example, 2 the clearance of the organic anion p-aminohippurate (PAH), about 40% of plasma Ca is bound to plasma proteins, so 2 infused intravenously. PAH is filtered and vigorously se- 60% of plasma Ca is freely filterable. At TmG, the limited number of tubule glucose carriers are all saturated and transport glucose at the maximal rate. The glucose threshold is not a fixed plasma concentration 800 but depends on three factors: GFR, TmG, and amount of splay. A low GFR leads to an elevated threshold because the filtered glucose load is reduced and the kidney tubules can Filtered reabsorb all the filtered glucose despite an elevated plasma 600 [glucose]. A reduced TmG lowers the threshold because the tubules have a diminished capacity to reabsorb glucose. One reason for splay is that not all nephrons have the same filtering and reabsorbing capaci- Splay ties. Thus, nephrons with relatively high filtration rates and 200 low glucose reabsorptive rates excrete glucose at a lower Excreted plasma concentration than nephrons with relatively low fil- Threshold tration rates and high reabsorptive rates. A second reason for splay is that the glucose carrier does not have an infi- 0 nitely high affinity for glucose, so glucose escapes in the 0 200 400 600 800 urine even before the carrier is fully saturated. An increase Plasma glucose (mg/dL) in splay results in a decrease in glucose threshold. In uncontrolled diabetes mellitus, plasma glucose levels The plasma [glucose] was elevated by infusing are abnormally elevated, and more glucose is filtered than glucose-containing solutions. Urinary excretion of glucose, gluco- unit time (top line) is determined from the product of the plasma suria, produces an osmotic diuresis. Excreted glucose (bot- in urine output; in osmotic diuresis, the increased urine flow tom line) is determined by measuring the urine [glucose] and flow results from the excretion of osmotically active solute. Reabsorbed glucose is calculated from the difference be- tween filtered and excreted glucose. Tm tubular transport abetes (from the Greek for “syphon”) gets its name from G maximum for glucose. Equations 8 and 9 for quantitating tubular transport The Tubular Transport Maximum for rates yield the net rate of reabsorption or secretion of a PAH Provides a Measure of Functional substance. It is possible for a single substance to be both Proximal Secretory Tissue reabsorbed and secreted; the equations do not give unidi- rectional reabsorptive and secretory movements, but only p-Aminohippurate is secreted only by proximal tubules in the net transport. At low plasma PAH concentrations, the rate of secretion increases linearly with the plasma [PAH]. At high plasma PAH concentrations, the secretory carriers are sat- The Glucose Titration Study Assesses urated and the rate of PAH secretion stabilizes at a constant Renal Glucose Reabsorption maximal value, called the tubular transport maximum for PAH (TmPAH). The TmPAH is directly related to the num- Insights into the nature of glucose handling by the kidneys ber of functioning proximal tubules and, therefore, pro- can be derived from a glucose titration study (Fig. Inulin is and excretion of PAH observed when the plasma [PAH] is infused to permit measurement of GFR and calculation of progressively elevated by intravenous infusion. The rate of glucose reabsorption is determined from the differ- ence between the filtered load and the rate of excretion. At RENAL BLOOD FLOW normal plasma glucose levels (about 100 mg/dL), all of the filtered glucose is reabsorbed and none is excreted. This allows them to the plasma [glucose] exceeds a certain value (about 200 filter the blood plasma at a high rate.

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By contrast cheap sildalis 120mg with visa, the superficial fascia under the skin of the back of the hand cheap 120 mg sildalis amex, elbow, and facial region is thin. The Deep fascia surrounds adjacent muscles, compartmentalizing and more movable bony attachment of the muscle, known as the in- binding them into functional groups. Subserous fascia extends be- sertion, is pulled toward its less movable attachment, the origin. Nerves and vessels In muscles associated with the girdles and appendages, the origin traverse subserous fascia to serve serous membranes. The fleshy, thickened portion of a muscle is referred to as The tenderness of meat is due in part to the amount of con- nective tissue present in a particular cut. An example is the galea aponeurotica, which is found and may present a social problem in trying to extract it discreetly on the top and sides of the skull (see fig. Attached to muscles generally do not contract separately but work as func- articulating bones, retinacula anchor groups of tendons and keep tional groups. Muscles that contract together in accomplishing a them from bowing during muscle contraction. Muscular System © The McGraw−Hill Anatomy, Sixth Edition Companies, 2001 Chapter 9 Muscular System 237 FIGURE 9. Muscular System © The McGraw−Hill Anatomy, Sixth Edition Companies, 2001 238 Unit 4 Support and Movement TABLE 9. Antagonistic muscles perform opposite functions and pendage are shortened. For exam- Seldom does the action of a single muscle cause a move- ple, the two heads of the biceps brachii muscle, together with the ment at a joint. Utilization of several synergistic muscles brachialis muscle, contract to flex the elbow joint. The triceps rather than one massive muscle allows for a division of labor. One brachii muscle, the antagonist to the biceps brachii and muscle may be an important postural muscle, for example, whereas brachialis muscles, extends the elbow as it is contracted. Antagonistic muscles are necessary because the fibers in a contracted muscle are shortened and must be elongated be- fore they can once again cause movement through another Muscle Architecture contraction. Gravity may also act as the antagonist for certain Skeletal muscles may be classified on the basis of fiber arrange- muscles. When an elevated upper appendage is relaxed, for ex- ment as parallel, convergent, sphincteral (circular), or pennate ample, gravity brings it down to the side of the body, and the (table 9. Each type of fiber arrangement provides the muscle with distinct capabilities. Muscle fiber architecture can be observed on a cadaver or other dissection specimen. If you have the opportunity to learn the muscles of the body from a cadaver, observe the fiber ar- synergistic: Gk. Muscular System © The McGraw−Hill Anatomy, Sixth Edition Companies, 2001 Chapter 9 Muscular System 239 Origins TABLE 9. When one antagonistic group contracts, and (c) multipennate the other one must relax; otherwise, movement does not occur. Muscle fibers will atrophy if they are not periodically stim- require extensive vascularity to receive nutrients and oxygen ulated to contract. Smaller muscles generally have a single artery supplying blood and perhaps two veins returning For years it was believed that muscle soreness was simply caused by a buildup of lactic acid within the muscle fibers blood (fig. The microscopic capillary exchange between arteries and factor related to soreness, recent research has shown that there is veins occurs throughout the endomysium that surrounds indi- also damage to the contractile proteins within the muscle. This means that there must be exten- microscopic damage causes an inflammatory response that re- sive innervation (served with neurons) to a muscle to ensure the sults in swelling and pain. If enough proteins are torn, use of the entire muscle may be compromised. Staying in good physical connection of each muscle fiber to a nerve cell. Actually there condition guards against muscle soreness following exercise. A motor (efferent) Conditioning the body not only improves vascularity but enlarges neuron is a nerve cell that conducts nerve impulses to the muscle muscle fibers and allows them to work more efficiently over a fiber, stimulating it to contract. Muscular System © The McGraw−Hill Anatomy, Sixth Edition Companies, 2001 240 Unit 4 Support and Movement FIGURE 9. Contrast the following terms: endomysium and epimysium; Objective 7 Distinguish between isotonic and isometric fascia and tendon; aponeurosis and retinaculum. Give some examples of synergistic muscles and Objective 8 Define motor unit and discuss the role of motor state which muscles are antagonistic. Skeletal Muscle Fibers Despite their unusual elongated shape, muscle cells have the SKELETAL MUSCLE FIBERS AND same organelles as other cells: mitochondria, intracellular mem- branes, glycogen granules, and so forth. Unlike most other cells TYPES OF MUSCLE CONTRACTION in the body, however, skeletal muscle fibers are multinucleated Muscle fiber contraction in response to a motor impulse results and striated (fig.