By K. Nerusul. Knox Theological Seminary.

C cheap sildalis 120mg visa erectile dysfunction pills thailand, The voltage-gated channel remains closed until when resistance is low buy cheap sildalis 120 mg line erectile dysfunction age 50. CHAPTER 3 The Action Potential, Synaptic Transmission, and Maintenance of Nerve Function 41 brane potential to change after a stimulus is applied is called gated sodium channels initiates an action potential. The ac- the time constant or , and its relationship to capacitance tion potential then propagates to the axon terminal, where (C) and resistance (R) is defined by the following equation: the associated depolarization causes the release of neuro- transmitter. The initial depolarization to start this process RC (2) derives from synaptic inputs causing ligand-gated channels In the absence of an action potential, a stimulus applied to open on the dendrites and somata of most neurons. For to the neuronal membrane results in a local potential peripheral sensory neurons, the initial depolarization re- change that decreases with distance away from the point of sults from a generator potential initiated by a variety of sen- stimulation. The voltage change at any point is a function sory receptor mechanisms (see Chapter 4). If a lig- and-gated channel opens briefly and allows positive ions to Characteristics of the Action Potential. Depolarization enter the neuron, the electrical potential derived from that of the axon hillock to threshold results in the generation current will be greatest near the channels that opened, and and propagation of an action potential. The action poten- the voltage change will steadily decline with increasing dis- tial is a transient change in the membrane potential charac- tance away from that point. The reason for the decline in terized by a gradual depolarization to threshold, a rapid ris- voltage change with distance is that some of the ions back- ing phase, an overshoot, and a repolarization phase. The leak out of the membrane because it is not a perfect insula- repolarization phase is followed by a brief afterhyperpolar- tor, and less charge reaches more distant sites. Since mem- ization (undershoot) before the membrane potential again brane resistance is a stable property of the membrane, the reaches resting level (Fig. The distance at which the initial transmembrane voltage change has fallen to 37% of its peak value is defined as the space constant or. The value of the space constant depends on the internal axo- plasmic resistance (Ra) and on the transmembrane resist- ance (Rm) as defined by the following equation: Rm/Ra (3) Rm is usually measured in ohm-cm and Ra in ohm/cm. Ra decreases with increasing diameter of the axon or dendrite; thus, more current will flow farther along inside the cell, and the space constant is larger. Similarly, if Rm increases, less current leaks out and the space constant is larger. The larger the space constant, the farther along the membrane a volt- age change is observed after a local stimulus is applied. Membrane capacitance and resistance, and the resultant time and space constants, play an important role in both the propagation of the action potential and the integration of incoming information. An Action Potential Is Generated at the Axon Hillock and Conducted Along the Axon An action potential depends on the presence of voltage- gated sodium and potassium channels that open when the neuronal membrane is depolarized. These voltage-gated channels are restricted to the axon of most neurons. Thus, neuronal dendrites and cell bodies do not conduct action potentials. In most neurons, the axon hillock of the axon has a very high density of these voltage-gated channels. In sensory neurons that convey information to the CNS from distant peripheral targets, the trigger zone is FIGURE 3. A, Depo- larization to threshold, the rising phase, over- in the region of the axon close to the peripheral target. B, Changes in sodium (gNa) and gated sodium channels open; as Na ions enter and cause potassium (g ) conductances associated with an action potential. At a The rising phase of the action potential is the result of an increase critical membrane potential called the threshold, incoming in sodium conductance, while the repolarization phase is a result Na exceeds outgoing K (through leakage channels), and of a decrease in sodium conductance and a delayed increase in the resulting explosive opening of the remaining voltage- potassium conductance. The voltage nels, as well as in voltage-gated calcium and chloride chan- measured is compared to that detected by a reference elec- nels, are now known to be the basis of several diseases of trode placed outside the cell. These diseases are collectively known as two measurements is a measure of the membrane potential. This technique is used to monitor the membrane potential at rest, as well as during an action potential. In most neurons, the axon hillock (initial segment) is the trigger zone that gen- Action Potential Gating Mechanisms. The membrane of the initial and repolarizing phases of the action potential can be ex- segment contains a high density of voltage-gated sodium plained by relative changes in membrane conductance and potassium ion channels.

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The underestimate of ECF volume because they are excluded ICF values are based on determinations made in skeletal from some of the extracellular water—for example buy generic sildalis 120mg line impotence zantac, the wa- muscle cells cheap sildalis 120mg on line doctor for erectile dysfunction in kolkata. These cells account for about two thirds of the ter in dense connective tissue and cartilage. Concentrations are expressed niques are required when using these sugars because they in terms of milliequivalents per liter or per kg H2O. For fusible anions (such as Cl ) are higher in interstitial fluid 2 2 singly charged (univalent) ions, such as Na , K , Cl , or than in plasma. For doubly charged (di- extent (about 40% and 30%, respectively) by plasma pro- 2 2 2– valent) ions, such as Ca , Mg , or SO4 , 1 mmol is equal teins, and it is only the unbound ions that can diffuse 2 to 2 mEq. Some electrolytes, such as proteins, are polyva- through capillary walls. The usefulness of ex- Mg concentrations are higher than in interstitial fluid. The cells have a higher K , Mg , and protein concentration than in the surrounding intersti- 3 cations 3 anions (4) 2 tial fluid. The intracellular Na , Ca , Cl , and HCO3 If we know the total concentration (mEq/L) of all cations levels are lower than outside the cell. The anions in skele- in a solution and know only some of the anions, we can eas- tal muscle cells labeled “Others” are mainly organic phos- ily calculate the concentration of the remaining anions. Na is the major cation in plasma, and Cl and [Na ] are a consequence of plasma membrane Na /K - HCO3 are the major anions. The plasma proteins (mainly ATPase activity; this enzyme extrudes Na from the cell serum albumin) bear net negative charges at physiological and takes up K. The electrolytes are actually dissolved in the plasma in skeletal muscle cells are primarily a consequence of the water, so the second column in Table 24. The water content of plasma is vors the outward movement of these small, negatively 2 usually about 93%; about 7% of plasma volume is occupied charged ions. The intracellular [Mg ] is high; most is not 2 by solutes, mainly the plasma proteins. Intracellular [Ca ] is 2 tration in plasma to concentration in plasma water, we di- low; as discussed in Chapter 1, the cytosolic [Ca ] in rest- 7 vided the plasma concentration by the plasma water con- ing cells is about 10 M (0. Therefore, 142 mEq Na /L Ca is sequestered in organelles, such as the sarcoplasmic plasma becomes 153 mEq/L H2O or 153 mEq/kg H2O reticulum in skeletal muscle. It contains all of the small electrolytes in es- Intracellular and Extracellular Fluids Are sentially the same concentration as in plasma, but little pro- Normally in Osmotic Equilibrium tein. The proteins are largely confined to the plasma Despite the different compositions of ICF and ECF, the to- because of their large molecular size. Differences in small tal solute concentration (osmolality) of these two fluid ion concentrations between plasma and interstitial fluid compartments is normally the same. ICF and ECF are in os- (compare Columns 2 and 3) occur because of the different motic equilibrium because of the high water permeability protein concentrations in these two compartments. Two of cell membranes, which does not permit an osmolality factors are involved. If the osmolality changes in one cause the plasma proteins are negatively charged, they compartment, water moves to restore a new osmotic equi- cause a redistribution of small ions, so that the concentra- librium (see Chapter 2). But the lat- added to an original total body water volume of 42 L, the ter depends on the amount of solute present and the osmo- new total body water volume is 44 L. This fact follows from the definition of the term con- so the new osmolality at equilibrium is (7,980 3,990 centration: concentration amount/volume; hence, volume mOsm)/44 kg 272 mOsm/kg H2O. The main osmotically active ICF at equilibrium, calculated by solving the equation, 272 solute in cells is K ; therefore, a loss of cell K will cause mOsm/kg H2O volume 7,980 mOsm, is 29. From these cal- motically active solute in the ECF is Na ; therefore, a gain culations, we conclude that two thirds of the added water or loss of Na from the body will cause the ECF volume to ends up in the cell compartment and one third stays in the swell or shrink, respectively. This description of events is artificial because, in real- The distribution of water between intracellular and ex- ity, the kidneys would excrete the added water over the tracellular compartments changes in a variety of circum- course of a few hours, minimizing the fall in plasma osmo- stances. The y-axis represents total solute concentration and lution) were added to the ECF. Isotonic saline is isosmotic the x-axis the volume; the area of a box (concentration to plasma or ECF and, by definition, causes no change in times volume) gives the amount of solute present in a com- cell volume. Note that the height of the boxes is always equal, in the ECF and there is no change in osmolality.

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Unlike the nonvascular granulosa cells in the THE MENSTRUAL CYCLE follicle purchase sildalis 120 mg online xeloda impotence, luteal cells have a rich blood supply proven 120 mg sildalis erectile dysfunction treatment without medicine. Invasion by capillaries starts immediately after the LH surge and is facil- Under normal conditions, ovulation occurs at timed inter- itated by the dissolution of the basement membrane be- vals. Sexual intercourse may occur at any time during the cy- tween theca and granulosa cells. Peak vascularization is cle, but fertilization occurs only during the postovulatory reached 7 to 8 days after ovulation. Once pregnancy occurs, ovulation ceases, and after Differentiated theca and stroma cells, as well as granulosa parturition, lactation also inhibits ovulation. The first men- cells, are incorporated into the corpus luteum, and all three strual cycle occurs in adolescence, usually around age 12. Although some progesterone is secreted first few cycles are usually irregular and anovulatory, as the before ovulation, peak progesterone production is reached 6 result of delayed maturation of the positive feedback by to 8 days after the LH surge. The life span of the corpus lu- estradiol on a hypothalamus that fails to secrete significant teum is limited. During puberty, LH secretion occurs more during within about 13 days after ovulation. During the menstrual periods of sleep than during periods of being awake, result- cycle, the function of the corpus luteum is maintained by ing in a diurnal cycle. An insufficient number of LH receptors progesterone to maintain pregnancy during its very early could be due to insufficient priming of the developing fol- stages. It is well known that FSH increases the num- nation include pelvic cramping and the detection of blood, ber of LH receptors in the follicle. If the corpus luteum have been inadequate in inducing full luteinization of the is truly deficient, then fertilization may occur around the ide- corpus luteum, yet there was sufficient LH to induce ovu- alized day 14 (ovulation), pregnancy will terminate during lation. It has been estimated that only 10% of the LH surge the deficient luteal phase, and menses will start on sched- is required for ovulation, but the amount required for full ule. Without measuring levels of hCG, the pregnancy detec- luteinization and adequate progesterone secretion to tion hormone, the woman would not know that she is preg- maintain pregnancy is not known. Luteal insufficiency is a common cause of infertil- the midluteal phase and do not match endometrial biop- ity. Women are advised to see their physician if pregnancy sies, exogenous progesterone may be administered in does not result after 6 months of unprotected intercourse. Other options include the induction of follic- the corpus luteum provides insights into this clinical prob- ular development and ovulation with clomiphene and lem. This treatment would likely produce a large, First, the number of luteinized granulosa cells in the corpus healthy, estrogen-secreting graafian follicle with suffi- luteum may be insufficient because of the ovulation of a cient LH receptors for luteinization. The exogenous hCG small follicle or the premature ovulation of a follicle that is given to supplement the endogenous LH surge and to was not fully developed. Second, the number of LH recep- ensure full stimulation of the graafian follicle, ovulation, tors on the luteinized granulosa cells in the graafian follicle adequate progesterone, and luteinization of the develop- and developing corpus luteum may be insufficient. CHAPTER 38 The Female Reproductive System 677 LH peak 50 50 40 40 30 30 FSH 20 20 10 10 LH 0 0 20 10 300 2 200 17-OH P 1 P 1 E2β 100 0 20 20 Luteal regression 10 10 Day: 0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 Menses Ovulation Phase: Menstrual Follicular Ovulatory Luteal Day of menstrual cycle FIGURE 38. The average menstrual cycle length in adult women is 28 ception and lactation and is subjected to modulation by days, with a range of 25 to 35 days. The interval from ovu- physiological, psychological, and social factors. In contrast, the interval from The Menstrual Cycle Requires Synchrony the onset of menses to ovulation (the follicular phase) is Among the Ovary, Brain, and Pituitary more variable and accounts for differences in cycle lengths among ovulating women. The menstrual cycle requires several coordinated elements: The menstrual cycle is divided into four phases hypothalamic control of pituitary function, ovarian follicu- (Fig. The menstrual phase, also called menses or lar and luteal changes, and positive and negative feedback menstruation, is the bleeding phase and lasts about 5 days. The ovarian follicular phase lasts about 10 to 16 days; folli- We have discussed separately the mechanisms that regulate cle development occurs, estradiol secretion increases, and the synthesis and release of the reproductive hormones; the uterine endometrium undergoes proliferation in re- now we put them together in terms of sequence and inter- sponse to rising estrogen levels. For this purpose, we use a hypothetical cycle of 28 24 to 48 hours, and the luteal phase lasts 14 days. During menstruation, estrogen, progesterone, and in- The cycles become irregular as menopause approaches hibin levels are very low as a result of the luteal regression around age 50, and cycles cease thereafter. During the re- that has just occurred and the low estrogen synthesis by im- productive years, menstrual cycling is interrupted by con- mature follicles.

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