scholarly journals Fine Gating Properties of Channels Responsible for Persistent Sodium Current Generation in Entorhinal Cortex Neurons

2002 ◽  
Vol 120 (6) ◽  
pp. 855-873 ◽  
Author(s):  
Jacopo Magistretti ◽  
Angel Alonso
Keyword(s):  
Entorhinal Cortex ◽  
Voltage Dependence ◽  
Burst Duration ◽  
The Other ◽  
Na Channel ◽  
Kinetic Properties ◽  
Channel Activity ◽  
Other Hand ◽  
Voltage Dependent ◽  
The Mean

The gating properties of channels responsible for the generation of persistent Na+ current (INaP) in entorhinal cortex layer II principal neurons were investigated by performing cell-attached, patch-clamp experiments in acutely isolated cells. Voltage-gated Na+-channel activity was routinely elicited by applying 500-ms depolarizing test pulses positive to −60 mV from a holding potential of −100 mV. The channel activity underlying INaP consisted of prolonged and frequently delayed bursts during which repetitive openings were separated by short closings. The mean duration of openings within bursts was strongly voltage dependent, and increased by e times per every ∼12 mV of depolarization. On the other hand, intraburst closed times showed no major voltage dependence. The mean duration of burst events was also relatively voltage insensitive. The analysis of burst-duration frequency distribution returned two major, relatively voltage-independent time constants of ∼28 and ∼190 ms. The probability of burst openings to occur also appeared largely voltage independent. Because of the above “persistent” Na+-channel properties, the voltage dependence of the conductance underlying whole-cell INaP turned out to be largely the consequence of the pronounced voltage dependence of intraburst open times. On the other hand, some kinetic properties of the macroscopic INaP, and in particular the fast and intermediate INaP-decay components observed during step depolarizations, were found to largely reflect mean burst duration of the underlying channel openings. A further INaP decay process, namely slow inactivation, was paralleled instead by a progressive increase of interburst closed times during the application of long-lasting (i.e., 20 s) depolarizing pulses. In addition, long-lasting depolarizations also promoted a channel gating modality characterized by shorter burst durations than normally seen using 500-ms test pulses, with a predominant burst-duration time constant of ∼5–6 ms. The above data, therefore, provide a detailed picture of the single-channel bases of INaP voltage-dependent and kinetic properties in entorhinal cortex layer II neurons.

NaCl-dependent expression of amiloride-blockable Na+ channel in Xenopus oocytes

1992 ◽  
Vol 262 (2) ◽  
pp. G244-G248 ◽  
Author(s):  
C. Asher ◽  
D. Singer ◽  
R. Eren ◽  
O. Yeger ◽  
N. Dascal ◽  
...  
Keyword(s):  
Xenopus Oocytes ◽  
The Other ◽  
Na Channel ◽  
Channel Activity ◽  
High Affinity ◽  
Other Hand ◽  
Exogenous Rna ◽  
Lower Intestine ◽  
Regulation Of Transport

RNA was isolated from chicken lower intestine (both colon and coprodeum) and injected into Xenopus oocytes. 22Na+ fluxes measured after 1-4 days demonstrated the induction of an amiloride-blockable pathway. The Na+ transporter expressed by the exogenous RNA had a high affinity to amiloride (inhibitory constant less than 0.1 microM), but was insensitive to ethylisopropyl amiloride, i.e., it is likely to be the apical Na+ channel. Functional channels were readily expressed in oocytes injected with RNA derived from chickens fed a low-NaCl diet. On the other hand, no channel activity was detected in oocytes injected with RNA isolated from chickens fed a high-NaCl diet. Thus the previously reported regulation of transport by the dietary NaCl intake involves modulations in the level of mRNA that codes either for the Na+ channel or a posttranscriptional regulator of the channel.

scholarly journals Kinetics of 9-aminoacridine block of single Na channels.

1984 ◽  
Vol 84 (3) ◽  
pp. 361-377 ◽  
Author(s):  
D Yamamoto ◽  
J Z Yeh
Keyword(s):  
Rate Constant ◽  
Voltage Dependence ◽  
Single Channel ◽  
Na Channel ◽  
Na Channels ◽  
Patch Clamp Technique ◽  
Open Time ◽  
Voltage Dependent ◽  
The Mean ◽  
Kinetics Of

The kinetics of 9-aminoacridine (9-AA) block of single Na channels in neuroblastoma N1E-115 cells were studied using the gigohm seal, patch clamp technique, under the condition in which the Na current inactivation had been eliminated by treatment with N-bromoacetamide (NBA). Following NBA treatment, the current flowing through individual Na channels was manifested by square-wave open events lasting from several to tens of milliseconds. When 9-AA was applied to the cytoplasmic face of Na channels at concentrations ranging from 30 to 100 microM, it caused repetitive rapid transitions (flickering) between open and blocked states within single openings of Na channels, without affecting the amplitude of the single channel current. The histograms for the duration of blocked states and the histograms for the duration of open states could be fitted with a single-exponential function. The mean open time (tau o) became shorter as the drug concentration was increased, while the mean blocked time (tau b) was concentration independent. The association (blocking) rate constant, kappa, calculated from the slope of the curve relating the reciprocal mean open time to 9-AA concentration, showed little voltage dependence, the rate constant being on the order of 1 X 10(7) M-1s-1. The dissociation (unblocking) rate constant, l, calculated from the mean blocked time, was strongly voltage dependent, the mean rate constant being 214 s-1 at 0 mV and becoming larger as the membrane being hyperpolarized. The voltage dependence suggests that a first-order blocking site is located at least 63% of the way through the membrane field from the cytoplasmic surface. The equilibrium dissociation constant for 9-AA to block the Na channel, defined by the relation of l/kappa, was calculated to be 21 microM at 0 mV. Both tau -1o and tau -1b had a Q10 of 1.3, which suggests that binding reaction was diffusion controlled. The burst time in the presence of 9-AA, which is the sum of open times and blocked times, was longer than the lifetime of open channels in the absence of drug. All of the features of 9-AA block of single Na channels are compatible with the sequential model in which 9-AA molecules block open Na channels, and the blocked channels could not close until 9-AA molecules had left the blocking site in the channels.

scholarly journals Agonist-specific voltage-dependent gating of lysosomal two-pore Na+ channels

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Xiaoli Zhang ◽  
Wei Chen ◽  
Ping Li ◽  
Raul Calvo ◽  
Noel Southall ◽  
...  
Keyword(s):  
Small Molecule ◽  
Membrane Trafficking ◽  
High Throughput Screening ◽  
Voltage Dependence ◽  
Na Channel ◽  
Dependent Manner ◽  
Na Channels ◽  
Channel Activity ◽  
Ph Homeostasis ◽  
Voltage Dependent

Mammalian two-pore-channels (TPC1, 2; TPCN1, TPCN2) are ubiquitously- expressed, PI(3,5)P2-activated, Na+-selective channels in the endosomes and lysosomes that regulate luminal pH homeostasis, membrane trafficking, and Ebola viral infection. Whereas the channel activity of TPC1 is strongly dependent on membrane voltage, TPC2 lacks such voltage dependence despite the presence of the presumed ‘S4 voltage-sensing’ domains. By performing high-throughput screening followed by lysosomal electrophysiology, here we identified a class of tricyclic anti-depressants (TCAs) as small-molecule agonists of TPC channels. TCAs activate both TPC1 and TPC2 in a voltage-dependent manner, referred to as Lysosomal Na+ channel Voltage-dependent Activators (LyNa-VAs). We also identified another compound which, like PI(3,5)P2, activates TPC2 independent of voltage, suggesting the existence of agonist-specific gating mechanisms. Our identification of small-molecule TPC agonists should facilitate the studies of the cell biological roles of TPCs and can also readily explain the reported effects of TCAs in the modulation of autophagy and lysosomal functions.

Effect on Polymer Chain Structure Caused by the Molar Fraction of 4-Hydroxybutyrate in Poly(3-hydroxybutyrate- co -4-hydroxybutyrate)

2012 ◽  
Vol 602-604 ◽  
pp. 776-780
Author(s):  
Zhi Qiang Li ◽  
Mei Li ◽  
Wei Jia Fan
Keyword(s):  
Molecular Weight ◽  
Intrinsic Viscosity ◽  
Polymer Chain ◽  
Molar Fraction ◽  
Chain Structure ◽  
The Other ◽  
Mean Square ◽  
Polarizing Microscope ◽  
Other Hand ◽  
The Mean

Poly(3-hydroxybutyrate-co-4-hydroxybutyrate)copolymer [P(3HB-co-4HB)] is a kind of biodegradable high molecular polymer produced by bioaccumulation. Because of the good biodegradability and biocompatibility, P(3HB-co-4HB)s have attracted wide attention . At first, the intrinsic viscosity[η] in good solvent of P(3HB-co-4HB) s with varying contents of 4HB was investigated in different temperature. Second, observed the changes of crystallization gathered state caused by the varying contents of 4HB by polarizing microscope. The results show that to the P(3HB-co-4HB)s in same molecular weight, the intrinsic viscosity[η] in good solvent barely changes when the mole fractions of 4HB increase. On the other hand, the mean square end to end distances[0] of macromolecular flexible chains increase with the mole fractions of 4HB. At the same time, the states of aggregation change from spherulites to dendrites. In this investigation, we discuss the reasons of the differences in depth.

scholarly journals Adult caddisflies (Trichoptera) attracted to artificial lights in the middle reaches of the Shinano River from 2005 to 2007

Zoosymposia ◽  
2011 ◽  
Vol 5 (1) ◽  
pp. 143-146 ◽  
Author(s):  
KIMIO HIRABAYASHI ◽  
GORO KIMURA ◽  
EISO INOUE
Keyword(s):  
Species Composition ◽  
Air Temperature ◽  
Large Scale ◽  
Abundant Species ◽  
The Other ◽  
Seasonal Abundance ◽  
Other Hand ◽  
The Mean ◽  
Summer Flood

The species composition and abundance of adult caddisflies attracted to the illuminated showcase of a vending machine set along the middle reaches of the Shinano River were investigated every Sunday night from April to November in 2005 to 2007. A total of 1,405 adult caddisflies was collected during the investigation periods. We identified a total of 13 species belonging to 11 genera of 8 families. The most abundant species was Psychomyia acutipennis (Ulmer 1908) each year. Psychomyia acutipennis adults were collected from mid-May to the beginning of October (the range of mean air temperature was 13.8 to 27.7°C), with its seasonal abundance divided into several peaks, i.e., the end of May, the beginning of June, and the end of August to the beginning of September in both 2006 and 2007. On the other hand, in 2005 when there was no large-scale summer flood and there were no marked abundance peaks. The present study suggests that the mean air temperature and summer floods impacted the seasonal abundance of P. acutipennis adults.

Allocation of Responsibility for Product Safety

1995 ◽  
Vol 39 (8) ◽  
pp. 435-439 ◽  
Author(s):  
Kenneth R. Laughery ◽  
David R. Lovvoll ◽  
Michael S. Wogalter
Keyword(s):  
Significant Interaction ◽  
User Study ◽  
Consumer Products ◽  
Product Safety ◽  
The Other ◽  
Product Use ◽  
Other Hand ◽  
High Hazard ◽  
The Mean

Three studies were carried out to explore how people allocate responsibility for safety during product use. In Study 1 29 consumer products were named and subjects apportioned safety responsibility to the manufacturer, the retailer, the user, and a potentially relevant organization not in the stream of commerce (e.g., FDA, CPSC, Underwriters Laboratories). The mean percent responsibility allocated to these four alternatives was 43%, 9%, 27% and 21% respectively. A significant interaction indicated that the allocation varied across products. In Study 2 safety responsibility for the same products was allocated to the manufacturer, retailer and user, but the “outside” organization was omitted. The mean percent allocated was 51%, 20% and 30% respectively. In this study, additional questions assessed various perceptions of the products and the subject's familiarity with the products. The results indicated that responsibility allocation was a function of perception of product hazardousness; the more hazardous a product is perceived to be, the more responsibility is allocated to the user. Study 3 investigated some of the attributes of high hazard products which are associated with various allocations of product safety. For high hazard products with open and obvious risks (chain saws, cutting torches), more responsibility was allocated to consumers as opposed to manufacturers. On the other hand, for those high hazard products with “hidden” risks (pesticides, antifreeze), manufacturers were typically allocated a much higher degree of responsibility.

Contribution to the Study of the Death-rate of Persons in Asylums

1879 ◽  
Vol 25 (109) ◽  
pp. 1-4
Author(s):  
Arthur Mitchell
Keyword(s):  
General Population ◽  
Death Rate ◽  
The Other ◽  
Other Hand ◽  
Different Ages ◽  
The Mean ◽  
General Community

In the population of Scotch Asylums, there are so few persons below the age of 10 years that, for practical purposes, it may be correctly said there are none. of the general community, on the other hand, 25·6 per cent. are persons below that age. It is clear, therefore, that the death-rate of the population of asylums cannot properly be compared with the death-rate of the general population. To make such a comparison it is necessary to deal only with the deaths occurring among the 74·4 per cent. of the general community who are above the age of 10 years. When this is done, it appears that the mean annual death-rate for the general population is 1·7 per cent. as compared with 8·3 per cent. for the population of asylums. These figures refer to the whole population of asylums, and to the whole of the general population above the age of 10 years; but in order to show the rates at which persons of different ages die in asylums, and the rates at which persons of corresponding ages die in the general community, the following table has been prepared. It is founded on 3,800 deaths occurring during the seven years, 1870–1876, in the Asylums of Scotland, which had a mean population of 6,421 during those years.

The effect of frontal eye field and superior colliculus lesions on saccadic latencies in the rhesus monkey

1987 ◽  
Vol 57 (4) ◽  
pp. 1033-1049 ◽  
Author(s):  
P. H. Schiller ◽  
J. H. Sandell ◽  
J. H. Maunsell
Keyword(s):  
Eye Movements ◽  
Superior Colliculus ◽  
Short Latency ◽  
The Other ◽  
Frontal Eye Field ◽  
Express Saccades ◽  
Unimodal Distribution ◽  
Other Hand ◽  
Eye Field ◽  
The Mean

Rhesus monkeys were trained to make saccadic eye movements to visual targets using detection and discrimination paradigms in which they were required to make a saccade either to a solitary stimulus (detection) or to that same stimulus when it appeared simultaneously with several other stimuli (discrimination). The detection paradigm yielded a bimodal distribution of saccadic latencies with the faster mode peaking around 100 ms (express saccades); the introduction of a pause between the termination of the fixation spot and the onset of the target (gap) increased the frequency of express saccades. The discrimination paradigm, on the other hand, yielded only a unimodal distribution of latencies even when a gap was introduced, and there was no evidence for short-latency "express" saccades. In three monkeys either the frontal eye field or the superior colliculus was ablated unilaterally. Frontal eye field ablation had no discernible long-term effects on the distribution of saccadic latencies in either the detection or discrimination tasks. After unilateral collicular ablation, on the other hand, express saccades obtained in the detection paradigm were eliminated for eye movements contralateral to the lesion, leaving only a unimodal distribution of latencies. This deficit persisted throughout testing, which in one monkey continued for 9 mo. Express saccades were not observed again for saccades contralateral to the lesion, and the mean latency of the contralateral saccades was longer than the mean latency of the second peak for the ipsiversive saccades. The latency distribution of saccades ipsiversive to the collicular lesion was unaffected except for a few days after surgery, during which time an increase in the proportion of express saccades was evident. Saccades obtained with the discrimination paradigm yielded a small but reliable increase in saccadic latencies following collicular lesions, without altering the shape of the distribution. Unilateral muscimol injections into the superior colliculus produced results similar to those obtained immediately after collicular lesions: saccades contralateral to the injection site were strongly inhibited and showed increased saccadic latencies. This was accompanied by a decrease of ipsilateral saccadic latencies and an increase in the number of saccades falling into the express range. The results suggest that the superior colliculus is essential for the generation of short-latency (express) saccades and that the frontal eye fields do not play a significant role in shaping the distribution of saccadic latencies in the paradigms used in this study.(ABSTRACT TRUNCATED AT 400 WORDS)

Sex Differences in Privacy Preferences

1987 ◽  
Vol 64 (3_suppl) ◽  
pp. 1239-1242 ◽  
Author(s):  
Darhl M. Pedersen
Keyword(s):  
College Students ◽  
Sex Differences ◽  
The Other ◽  
Three Dimensions ◽  
Female College Students ◽  
Female College ◽  
Privacy Preferences ◽  
Other Hand ◽  
The Mean

A Privacy Questionnaire was administered to 118 male and 142 female college students to determine differences in the patterns of privacy preferences between the sexes. The questionnaire contained factor scales for measuring six independent types of privacy. t-tests showed that the means for women were significantly higher than those for men in their preferences for Intimacy with Family and Intimacy with Friends. On the other hand, for Isolation the mean for men was significantly higher than that for women. There were no significant differences between the means for the two sexes on the remaining three dimensions, Reserve, Solitude, and Anonymity.

scholarly journals Inactivation of N-type calcium current in chick sensory neurons: calcium and voltage dependence.

1994 ◽  
Vol 104 (2) ◽  
pp. 311-336 ◽  
Author(s):  
D H Cox ◽  
K Dunlap
Keyword(s):  
Voltage Dependence ◽  
Kinetic Properties ◽  
Dependent Manner ◽  
Slow Inactivation ◽  
Fast Inactivation ◽  
Drg Neurons ◽  
Rapid Phase ◽  
Dependent Inactivation ◽  
Voltage Dependent ◽  
Dependent Processes

We have studied the inactivation of high-voltage-activated (HVA), omega-conotoxin-sensitive, N-type Ca2+ current in embryonic chick dorsal root ganglion (DRG) neurons. Voltage steps from -80 to 0 mV produced inward Ca2+ currents that inactivated in a biphasic manner and were fit well with the sum of two exponentials (with time constants of approximately 100 ms and > 1 s). As reported previously, upon depolarization of the holding potential to -40 mV, N current amplitude was significantly reduced and the rapid phase of inactivation all but eliminated (Nowycky, M. C., A. P. Fox, and R. W. Tsien. 1985. Nature. 316:440-443; Fox, A. P., M. C. Nowycky, and R. W. Tsien. 1987a. Journal of Physiology. 394:149-172; Swandulla, D., and C. M. Armstrong. 1988. Journal of General Physiology. 92:197-218; Plummer, M. R., D. E. Logothetis, and P. Hess. 1989. Neuron. 2:1453-1463; Regan, L. J., D. W. Sah, and B. P. Bean. 1991. Neuron. 6:269-280; Cox, D. H., and K. Dunlap. 1992. Journal of Neuroscience. 12:906-914). Such kinetic properties might be explained by a model in which N channels inactivate by both fast and slow voltage-dependent processes. Alternatively, kinetic models of Ca-dependent inactivation suggest that the biphasic kinetics and holding-potential-dependence of N current inactivation could be due to a combination of Ca-dependent and slow voltage-dependent inactivation mechanisms. To distinguish between these possibilities we have performed several experiments to test for the presence of Ca-dependent inactivation. Three lines of evidence suggest that N channels inactivate in a Ca-dependent manner. (a) The total extent of inactivation increased 50%, and the ratio of rapid to slow inactivation increased approximately twofold when the concentration of the Ca2+ buffer, EGTA, in the patch pipette was reduced from 10 to 0.1 mM. (b) With low intracellular EGTA concentrations (0.1 mM), the ratio of rapid to slow inactivation was additionally increased when the extracellular Ca2+ concentration was raised from 0.5 to 5 mM. (c) Substituting Na+ for Ca2+ as the permeant ion eliminated the rapid phase of inactivation. Other results do not support the notion of current-dependent inactivation, however. Although high intracellular EGTA (10 mM) or BAPTA (5 mM) concentrations suppressed the rapid phase inactivation, they did not eliminate it. Increasing the extracellular Ca2+ from 0.5 to 5 mM had little effect on this residual fast inactivation, indicating that it is not appreciably sensitive to Ca2+ influx under these conditions.(ABSTRACT TRUNCATED AT 400 WORDS)

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