In whole-cell recordings from mammalian CNS neurons, AMPA-preferring glutamate receptors exhibit strong desensitization in response to AMPA, glutamate, and quisqualate, but not kainate or domoate. Such is reduced by lectins, the nootropic drug aniracetam, diazoxide. None of these compounds strongly modulate responses domoate, consistent with apparent lack agonists. We now report experiments on hippocampal neurons which were potentiated cyclothiazide, a benzothiadiazine diuretic...

Abstract In unanesthetized spinal cats an i.v. injection of DOPA depresses transmission short latency effects from the flexor reflex afferents (FRA), including excitatory and inhibitory action to motoneurones ascending pathways as well primary afferent terminals. The depression resembles that decerebrate preparation. After evoked by natural stimulation skin is increased. This increase due a long latency, lasting discharge in repetitive activity FRA. late accompanied wave depolarization...

1. Responses to the excitatory amino acids kainate, quisqualate, N-methyl-D-aspartate (NMDA), L-glutamate and L-aspartate were recorded in mouse hippocampal neurones cell culture, using whole-cell configuration of patch clamp technique. Agonists applied rapidly from an array flow pipes each 250 microns diameter, positioned within 100 nerve body. 2. NMDA, low concentrations L-glutamate, with glycine extracellular fluid, strongly antagonized by 50 microM-zinc. glycine-free solution, responses...

A fast perfusion system was used to apply excitatory amino acids embryonic hippocampal neurons grown in dissociated culture and voltage clamped the whole-cell recording configuration. Responses quisqualic acid DL-alpha-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic (AMPA; a potent quisqualate-like agonist) showed rapid desensitization: at 100 microM peak inward current declined plateau response on average 0.2 times (mean time constant, 30 ms). L-aspartic N-methyl-D-aspartic also microM, when...

1. Responses to N‐methyl‐D‐aspartic acid (NMDA) were recorded from mouse embryonic hippocampal neurones in dissociated culture, using whole‐cell patch‐clamp recording. A fast perfusion system, with an exchange time constant of less than 10 ms, was used study modulation NMDA receptor desensitization by glycine. 2. The onset well fitted a single‐exponential function; 30 nM‐glycine the 250 corresponding rate 4 s‐1. became faster increasing glycine concentration, slope 0.87 x 10(7) M‐1 Recovery...

The vanilloid receptor [transient potential (TRP)V1, also known as VR1] is a member of the TRP channel family. These receptors share significant sequence homology, similar predicted structure with six transmembrane-spanning domains (S1–S6), pore-forming region between S5 and S6, cytoplasmically oriented C- N-terminal regions. Although structural/functional studies have identified some key amino acids influencing gating TRPV1 ion channel, possible contributions terminal regions to function...

1. Responses to N-methyl-D-aspartic acid (NMDA) were recorded from mouse embryonic hippocampal neurones in dissociated culture, using the tight-seal, whole-cell, patch-clamp technique for voltage clamp. A rapid perfusion system, with an exchange time constant of less than 10 ms, was used apply NMDA under conditions which minimized slow, calcium-sensitive desensitization. With no added glycine, responses 100 microM-NMDA applied 1.5 s declined by greater 90%, due additional component...

The glutamate receptor gene GluR-4 is proposed to generate two spliced isoforms (Sommer et al., 1990). Screening a rat cerebellar cDNA library, we have now identified third type of transcript derived from by differential RNA processing. This encodes protein with "flop" module between transmembrane regions 3 and 4, but C-terminus segment 36 amino acids different the previously described flip/flop cDNAs. subunit was therefore designated as GluR-4c flop. Transcripts synthesized in vitro form...

1. The whole‐cell and outside‐out configurations of the patch‐clamp technique were used to record responses excitatory amino acids in mouse hippocampal neurones cell culture at different pH. kainate, quisqualate, N‐methyl‐D‐aspartate (NMDA) L‐glutamate applied by a rapid perfusion system. 2. In recording mode NMDA or low concentrations glutamate, recorded absence Mg2+ with glycine extracellular superfusion solution, antagonized acidic pH potentiated an alkaline solution. Decrease from 7.3...

1. Changes of extracellular K + concentration, [K] e , arising in the spinal cord cat response to an afferent stimulation were studied by means ‐specific micro‐electrodes. 2. In most active areas a single volley large input like common peroneal nerve or posterior tibial produced transient increase 0·05–0·1 m M which reached its peak 0·2–0·3 sec and it declined about 3 sec. 3. Much higher increases found during repetitive input. The highest (by ) was at 100 Hz, but even 1 Hz significant 0·25...

Fluorescence quenching is a powerful technique used to obtain information about the dynamic changes of proteins in complex macromolecular systems. In this work, graphene shown be very efficient quencher fluorescence molecules where effect was one order magnitude higher than that gold. The intensity distance-dependent increasing distance between molecule and surface from 4 7 nm increased by factor 7.5. This type dependence suggests nonradiative nature energy transfer fluorophore due...

1. By means of K‐specific double‐barrelled micro‐electrodes the time course changes in K+ concentration extracellular space lumbar spinal cord was examined after peripheral tetanic stimulation and a single volley mixed nerve non‐anaesthetized, intercollicularly decerebrated spinalized cats. 2. Tetanic (100 Hz) which increases [K]e from 3 to 9 mM is followed by phase reduced during decreases 0.5 below resting level, lasting 1–2 minutes before returning its original level. Evidence presented...

1. The multiply innervated anterior latissimus dorsi (ALD) and the focally posterior (PLD) muscles of chick were investigated 2-18 months after nerve cross-union.2. fast PLD muscle re-innervated by slow became supplied with ;en grappe' end-plates responded to a single volley local potentials only. Control original nerve, had plaque' synchronous action in same way as normal muscles.3. In ALD ;mixed' type innervation electromyographic response remained practically unchanged, exception...

Key points NMDA receptors (NMDARs) are tetrameric cation channels permeable to calcium; they mediate excitatory synaptic transmission in the CNS and their excessive activation can lead neurodegeneration. Although these direct contact with plasma membrane, lipid–NMDAR interactions little understood. Using cultured rat cerebellar granule cells, we show that acute chronic pretreatments resulting cell cholesterol depletion profoundly diminish NMDAR responses increase desensitization, also...

1. The whole‐cell configuration of the patch clamp method was used to record from hippocampal neurones in cell culture. Synaptic responses were evoked by loose stimulation adjacent presynaptic low‐density cultures. Agonists and antagonists applied rapidly, using an array flow pipes each diameter 250 microns, positioned within 100 microns postsynaptic neurone. 2. Bath application 50 microM‐zinc produced prolonged periods synaptic barrage action potential discharge. Flow pipe microM‐zinc,...

1. Mouse hippocampal neurons in dissociated culture were grown at low density on previously plated glial cell cultures and voltage clamped using the tight seal whole-cell patch-clamp technique. Flow pipes used to rapidly exchange extracellular solution, apply N-methyl-D-aspartic acid (NMDA) some NMDA antagonists. Fluctuation analysis was estimate changes behavior of NMDA-activated ion channels during application In presence control spectra well fit by single Lorentzian functions consistent...

The rationale for the topical application of capsaicin and other vanilloids in treatment pain is that such compounds selectively excite subsequently desensitize nociceptive neurons. This desensitization triggered by activation vanilloid receptors (TRPV1), which leads to an elevation intracellular free Ca2+ levels. Depending on concentration duration exposure, influx via TRPV1 desensitizes channels themselves, may represent not only a feedback mechanism protecting cell from toxic overload,...

Abstract In unanaesthetized spinal cats, injected with 1‐DOPA, volleys in the flexor reflex afferents (FRA) evoke a long latency, lasting dorsal root potential (DRP). Measurements of excitability ispilateral primary afferent terminals show corresponding depolarization Ia, but not Ib or cutaneous, terminals. Volleys FRA have no effect on Ia normal acute cat, presumably because neuronal pathway transmitting from to is inhibited by activity another FRA. Results are presented showing that after...