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Differential effects of enflurane on Glu- and ACH-induced chloride currents in Aplysia neurons 总被引:1,自引:0,他引:1
The primary site of anesthetic action remains controversial. In addition to non-specific actions of hydrophobic substances on the membrane, specific effects of volatile anesthetics on neuronal activity have been reported. In the present study, effects of enflurane on the chloride currents (ICl) induced by L-glutamic acid (Glu) and acetylcholine (ACh) in isolated Aplysia neurons were examined, using the 'concentration clamp' technique. Enflurane increased the peak amplitude of the ICl induced by low concentrations of Glu but decreased those evoked by higher concentrations of the agonist. The anesthetic accelerated both activation and desensitization phases of the Glu-induced ICl. On the other hand, the ACh-induced ICl in the same neuron was depressed in an uncompetitive manner in the presence of enflurane. The desensitization phase was not affected, although the activation phase became more rapid and the mean open time obtained by noise analysis was shortened. These results suggest the existence of specific steps in the process of activation and desensitization of channels, at which the volatile anesthetic exerts differential effects on the postsynaptic currents. 相似文献
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The effects of hydrogen ion concentration on the simplest steady-state enzyme systems 总被引:5,自引:5,他引:0
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P. Ottolenghi 《The Biochemical journal》1971,123(3):445-453
Laidler (1955) showed that consideration of the effect of pH on enzymic mechanisms that obey steady-state kinetics leads to the inclusion in the equations of a ;perturbation term' that can introduce curvature into the Lineweaver-Burk plots. He also stated conditions in which this term vanishes. This term can lead to apparent activation by substrate. Further, several cases are shown in which simplification, but not disappearance, of the perturbation term can lead to linearity of Lineweaver-Burk plots. These cases arise when the ionization of groups at the active site either is unaffected or is completely prevented when the enzyme-substrate complex is formed. It is also shown that V((app.)) can vary with pH without a concomitant change in K(m(app.)) in certain cases that obey steady-state kinetics without implying that K(m)=K(s). When the perturbation term is significant, Dixon's (1953) rules for the calculation of pK values will not always apply. 相似文献
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John G. McColl 《Biogeochemistry》1990,10(1):29-36
Hydrogen ion concentration, [H+], of discharge water from Pardee reservoir in the central Sierra Nevada, California was greater than expected in years of El Nino occurrence over the period 1954–86. This pattern is in addition to the general increase in [H+] over the same period attributed to acidic atmospheric deposition. Monthly means of [H+] also show differences between El Nino and non-El Nino years. Total annual runoff does not seem to be a controlling factor; the source and timing of storms are probably more important. Storms are usually from the west or northwest, but during El Nino years tropical-like storms from a more-southerly direction appear to carry acidic pollutants to the central Sierra Nevada. 相似文献
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Generation of the action potentials (AP) necessary to activate skeletal muscle fibers requires that inward membrane currents exceed outward currents and thereby depolarize the fibers to the voltage threshold for AP generation. Excitability therefore depends on both excitatory Na+ currents and inhibitory K+ and Cl- currents. During intensive exercise, active muscle loses K+ and extracellular K+ ([K+]o) increases. Since high [K+]o leads to depolarization and ensuing inactivation of voltage-gated Na+ channels and loss of excitability in isolated muscles, exercise-induced loss of K+ is likely to reduce muscle excitability and thereby contribute to muscle fatigue in vivo. Intensive exercise, however, also leads to muscle acidification, which recently was shown to recover excitability in isolated K(+)-depressed muscles of the rat. Here we show that in rat soleus muscles at 11 mM K+, the almost complete recovery of compound action potentials and force with muscle acidification (CO2 changed from 5 to 24%) was associated with reduced chloride conductance (1731 +/- 151 to 938 +/- 64 microS/cm2, P < 0.01) but not with changes in potassium conductance (405 +/- 20 to 455 +/- 30 microS/cm2, P < 0.16). Furthermore, acidification reduced the rheobase current by 26% at 4 mM K+ and increased the number of excitable fibers at elevated [K+]o. At 11 mM K+ and normal pH, a recovery of excitability and force similar to the observations with muscle acidification could be induced by reducing extracellular Cl- or by blocking the major muscle Cl- channel, ClC-1, with 30 microM 9-AC. It is concluded that recovery of excitability in K(+)-depressed muscles induced by muscle acidification is related to reduction in the inhibitory Cl- currents, possibly through inhibition of ClC-1 channels, and acidosis thereby reduces the Na+ current needed to generate and propagate an AP. Thus short term regulation of Cl- channels is important for maintenance of excitability in working muscle. 相似文献
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J. P. Danaceau M. T. Lucero 《Journal of comparative physiology. A, Neuroethology, sensory, neural, and behavioral physiology》1998,183(2):225-235
Isolated olfactory receptor neurons from the squid Lolliguncula brevis respond to betaine, a repellent odorant, with hyperpolarizing receptor potentials. Using perforated-patch techniques, we
determined that the hyperpolarizing conductance was selective for Cl− and could be reversibly blocked by the Cl− channel blockers 4-acetamido-4′-isothio-cyanatistilbene-2,2′disulfonic acid and niflumic acid. Gramicidin-patch recordings
revealed that [Cl−]i in squid olfactory receptor neurons is normally very low compared to vertebrate olfactory receptor neurons, and that activating
a Cl− conductance would hyperpolarize the cell in vivo. The lack of dependence on internal or external K+ or Na+ ruled out the possibility that the Cl− conductance was generated by a cation-dependent cotransporter or pump. Common G-protein-dependent signalling pathways, including
phospholipase C, arachidonic acid, and cyclic nucleotides, do not appear to be involved. Ca2+ imaging experiments showed that betaine did not affect [Ca2+]i, suggesting that the Cl− current is not Ca2+ dependent. Our findings represent the first report of an odorant-activated, hyperpolarizing chloride conductance in olfactory
receptor neurons.
Accepted: 20 March 1998 相似文献
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Effects of ammonium and bicarbonate-CO2 on intracellular chloride levels in Aplysia neurons.
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J M Russell 《Biophysical journal》1978,22(1):131-137
The level of intracellular free chloride in Aplysia giant neurons can be made to decline by pretreatment with 50 mM NH4+ solution followed by washing with 10 mM HCO3-/0.4% CO2-containing fluids. This effect can be completely blocked by the anion flux inhibitor, 4-acetamido-4'-isothiocyano-stilbene-2,2'-disulfonic acid (SITS). The net change of free chloride in the cell cannot be explained by changes in the electrochemical gradient of chloride. These results support the hypothesis that at least one mechanism for intracellular pH regulation involves a Cl-/HCO-3 exchange process. 相似文献
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Carlos Alonso-Alvarez Sophie Bertrand Godefroy Devevey Josiane Prost Bruno Faivre Gabriele Sorci 《Ecology letters》2004,7(5):363-368
In iteroparous species high investment in current reproduction is usually paid in terms of reduced future reproduction and increased mortality. However, the proximal mechanisms of these costs remain poorly understood. Free radicals arising as by‐products of normal metabolic activities have deleterious effects on cellular proteins, lipids and DNA, and this phenomenon is known as oxidative stress. Since reproduction is an energetically demanding activity, which increases both basal and field metabolic rates, one could expect that breeding effort generates an oxidative stress whose strength depends on the availability and efficiency of antioxidant defences. In agreement with this prediction, we show here for the first time that reproduction decreases antioxidant defences, illustrating that oxidative stress represents a cost of reproduction. We suggest that increased susceptibility to oxidative stress might be a general proximal connection between reproduction and survival underlying other mechanistic links previously acknowledged. 相似文献
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We have previously shown that lobster olfactory receptor neurons (ORNs) express an odorant-suppressible Cl(-) conductance that modulates the output of the cells. Here, we develop a more complete pharmacological profile of this conductance, showing it is blockable by the Cl(-) channel blockers DIDS, 9-AC and flufenamic acid, but not by niflumic acid. We then show that a conductance with this pharmacological profile is mediated by cyclic nucleotide signaling. These findings further our understanding of the cellular mechanisms through which odorants can modulate the output of lobster ORNs. 相似文献
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The double C2 domain protein family (DOC2) is characterized by two calcium-binding domains (C2). Upon binding to calcium, the affinity of the protein to phospholipids is significantly increased, leading to translocation of the protein from the cytosol to the plasma membrane. These properties, and the binding domain of DOC2B to Munc13, suggested that DOC2B could play a role in augmentation and potentiation of synaptic release. Nevertheless, the level of the free intracellular calcium concentration ([Ca(2+)](i)) which triggers its translocation under in vivo conditions, is not known. Using cultured Aplysia neurons that express rat EGFP-DOC2B, we found that the [Ca(2+)](i) increment necessary to induce EGFP-DOC2B translocation is approximately 200 nM in the bulk of the cytoplasm. The rate of EGFP-DOC2B recruitment to the plasma membrane is slower than the [Ca(2+)](i) elevation rate, while the detachment of EGFP-DOC2B from it is faster than the calcium removal. The extent of EGFP-DOC2B translocation to the plasma membrane reflects local submembrane [Ca(2+)](i). Our observations are consistent with the view that DOC2B can participate in the regulation of neurotransmitter release. It should be noted that EGFP-DOC2B could be used as a tool to map sub-membrane calcium dynamics under physiological conditions. 相似文献
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John M. Russell Douglas C. Eaton Malcolm S. Brodwick 《The Journal of membrane biology》1977,37(1):137-156
Summary Two methods were used to study effects of the antibiotic, nystatin, on giant neurons ofAplysia. In the first method the effects of various concentrations of nystatin on the current-voltage relationship were evaluated at a fixed time after exposure to the antibiotic using a two-microelectrode voltage clamp. Nystatin increased membrane conductance in a dose-dependent manner. The dose-response relation was very steep, with little or no effect below 15 mg/liter and an effect too large to measure at concentrations greater than 30 mg/liter. Upon return to antibiotic-free solution, membrane conductance returned to pre-treatment levels within 30 minutes. The second type of experiment involved use of ion-specific microelectrodes to measure changes of intracellular univalent ion activities which attended the nystatin-induced permeability. meability was also increased. Nystatin may therefore be used to selectively rearrange the internal ionic milieu to study the effect of such a change on membrane tranpsort or electrical properties. 相似文献
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Kowalchuk J. M.; Heigenhauser G. J.; Lindinger M. I.; Sutton J. R.; Jones N. L. 《Journal of applied physiology》1988,65(5):2080-2089
To assess the importance of factors influencing the resolution of exercise-associated acidosis, measurements of acid-base variables were made in nine healthy subjects after 30 s of maximal exercise on an isokinetic cycle ergometer. Quadriceps muscle biopsies (n = 6) were taken at rest, immediately after exercise, and at 3.5 and 9.5 min of recovery; arterial and femoral venous blood were sampled (n = 3) over the same time. Intracellular and plasma inorganic strong ions were measured by neutron activation and ion-selective electrodes, respectively; lactate concentration ([La-]) was measured enzymatically, and plasma PCO2 and pH were measured by electrodes. Immediately after exercise, intracellular [La-] increased to 47 meq/l, almost fully accounting for a reduction in intracellular strong ion difference ([SID]) from 154 to 106 meq/l. At the same time, femoral venous PCO2 increased to 100 Torr and plasma [La-] to 9.7 meq/l; however, plasma [SID] did not change because of a concomitant increase in inorganic [SID] secondary to increases in [K+], [Na+], and [Ca2+]. During recovery, muscle [La-] fell to 26 meq/l by 9.5 min; [SID] remained low (101 and 114 meq/l at 3.5 and 9.5 min, respectively) due almost equally to the elevated [La-] (30 and 26 meq/l) and reductions in [K+] (from 142 meq/l at rest to 123 and 128 meq/l). Femoral venous PCO2 rose to 106 Torr at 0.5 min postexercise and fell to resting values at 9.5 min.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
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Characteristics of pacemaker oscillations in Aplysia neurons 总被引:2,自引:0,他引:2