1,107 research outputs found
Trifluoperazine reduces inward ionic currents and secretion by separate mechanisms in bovine chromaffin cells
No full textUsing patch-clamp techniques, excitation and secretion in chromaffin cells were studied by measurement of unitary inward currents and of stimulus-evoked increments in membrane capacitance. The effect of the calmodulin inhibitor trifluoperazine (TFP) on Na, Ca and acetylcholine-induced (ACh) currents as well as on capacitance increments was investigated. TFP in concentrations up to 10 microM had no effect on Na channel currents. TFP was a potent anticholinergic agent. TFP in concentrations of 100 nM-1 microM decreased net ACh-induced currents by a slow block or allosteric modification of the channel. The effect was only partially reversible. Recovery from desensitization was retarded in direct relation to [TFP]. At the single channel level, TFP was found to slightly shorten open times in 0.5 and 20 microM-ACh. As reported previously, desensitization can be modelled by at least two desensitized states, as reflected by the bursting and clustering behaviour of single channels. TFP shortened clusters mainly by reducing the number of bursts per cluster. Whole-cell Ca currents (ICa) were reduced in 10 microM-TFP from an average of 29 microA cm-2-13 microA cm-2. Changes in capacitance of 1-200 fF were elicited in controls by maximal activation of the Ca current. We interpreted these steps to be the summed result of many exocytotic vesicular fusion events. Capacitance steps depended on ICa and were absent when extracellular Ca was removed. Application of 10 microM-TFP inhibited capacitance steps. The block of capacitance steps by TFP was shown to be independent of the reduction of ACh and Ca inward ionic currents. We conclude that the prevention of exocytosis by TFP is not completely described by its inhibition of electrical excitability but also results from intracellular actions
Substance P reduces acetylcholine-induced currents in isolated bovine chromaffin cells
No full textPatch-clamp techniques were used to examine the effect of substance P on acetylcholine-induced current in bovine chromaffin cells. Cells had been enzymatically isolated and kept in short-term culture. Experiments were performed at 22 degrees C. Under whole-cell voltage-clamp conditions substance P alone (2-10 microM) did not induce ionic currents. Acetylcholine (ACh, 20 microM) at -60 mV induced an inward current that desensitized in the continued presence of ACh. The time course of desensitization was somewhat variable from cell to cell. In most cases it could be fitted by a single exponential with time constant of 8-10 s. Substance P (2-50 microM) applied simultaneously with ACh induced what appeared to be an acceleration of the desensitization process. The time course in the presence of 10 microM-substance P (20 microM-ACh) was best fitted by the sum of two exponentials with time constants of 0.6 s and 5 s respectively. The effect was reversible. The recovery of ACh-induced current from desensitization was not affected by substance P. The time constant for recovery was approximately 7 s in the presence or absence of substance P. Single-channel records showed that the conductance of individual channels was not changed by substance P. The mean open time of single channels was shortened by substance P both at high (20 microM) and at low (0.5 microM) concentrations of ACh. The inverse mean open time varied linearly with substance P concentration. Single-channel responses appeared in bursts and clusters after almost complete desensitization at 20 microM-ACh, as was previously observed in frog skeletal muscle. Substance P dramatically reduced ACh current by increasing interburst intervals while decreasing burst duration and the number of openings per burst. We conclude that substance P inhibits ACh-induced depolarization of chromaffin cells either by increasing the rate of desensitization or by inducing channel blockade, which indirectly enhances desensitization. Possible models of desensitization in the absence and presence of substance P are discussed
Chloride channels in the nuclear membrane
No full textChloride-selective ion channels were measured from isolated rat liver nuclei. Single ion channel currents were recorded in both "nuclear-attached" and in excised patches in the inside-out configuration of the patch-clamp technique. Two types of chloride conductance were defined, a large conductance (150 pS; iCl,N) channel with complex kinetics and multiple substates, and a second smaller conductance (58 pS;ICln) channel sensitive to block by ATP. The channels were inhibited by pharmacological agents known to block chloride channels and were insensitive to internal and external changes in calcium and magnesium. Presumably the channels reside in the external membrane of the nuclear double membrane and may mediate charge balance in the release and uptake of calcium from the perinuclear space
Assessment and testing.
No full textIn this brief article, I discuss the relationship between language testing and the other sub-disciplines of applied linguistics and also the relationship, as I see it, between testing and assessment. The article starts with a brief exploration of the term ‘applied linguistics’ and then goes on to discuss the role of language testing within this discipline, the relationship between testing and teaching, and the relationship between testing and assessment. The second part of the article mentions some areas of current concern to testers and discusses in more detail recent advances in the areas of performance testing, alternative assessment, and computer assessment. One of my aims in this article is to argue that the skills involved in language testing are necessary not only for those constructing all kinds of language proficiency assessments, but also for those other applied linguists who use tests or other elicitation techniques to help them gather language data for research
Producing the docile body: analysing Local Area Under-performance Inspection (LAUI)
No full textSir Michael Wilshaw, the head of the Office for Standards in Education (OfSTED), declared a 'new wave' of Local Area Under-performance Inspections (LAUI) of schools 'denying children the standard of education they deserve'. This paper examines how the threat of LAUI played out over three mathematics lessons taught by a teacher in her first year in the profession. A Foucauldian approach is mobilised with regard to disciplinary power and 'docile bodies'. The paper argues that, in the case in point, LAUI was a tool mediating performative conditions and, ultimately, the docile body. The paper will be of concern to policy sociologists, teachers, school leaders, and those interested in school inspection
A. El Manira, W. Zhang, E. Svensson, N. Bussieres, J. Neurosci. 17, 1786 (1997).
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