Membrane currents induced by capsaicin (CAPS) in cultured sensory neurons from 1- to 2-day-old rats were studied. Responses to CAPS (lO^M) exceeding 1 nA at -50 mV were found in smaller, usually bipolar or tripolar neurons in which GABA (30 yuM) induced small or no response. Large, unipolar neurons, which exhibited large responses to GABA, were completely insensitive to CAPS (10//M). In contrast to GABA, responses to CAPS exhibited a slow rise and slow decay and a marked tachyphylaxis after repeated CAPS applications at high concentrations which made it difficult to study the concentration-response relationship. In partially run-down neurons, which exhibited quasi stable responses, the slope of the ascending phase was concentration-dependent with an apparent association rate constant Ki 9x104 [M-1s-1]. The time constant of the decay was 3.5 s, and was concentration-independent. However, in 5 neurones the EC50 measured from the first series of CAPS applications at increasing concentrations was 0.31 ±0.5ptA with a Hill coefficient 1.66±0.35. The responses to CAPS reversed at +10.4±2.5 mV suggesting that the current is carried nonselectively by monovalent cations and Ca2+. The channel conductance of CAPS-gated channels at -50 mV calculated from the mean membrane current and variance of the current noise in outside-out patches or measured directly was 28 pS (n=5). It is suggested that the CAPS-gated channels are either controlled by receptors with a very high affinity or that the channels are controlled by membrane-bound protein(s) which do not depend in their function on the supply of GTP or other intracellular metabolites.
Parvalbumin (PV) is a calcium-binding protein that is expressed by numerous neuronal subpopulations in the central nervous system. Staining for PV was often used in neuroanatomical studies in the past. Recently, several studies have suggested that PV acts in neurons as a mobile endogenous calcium buffer that affects temporo-spatial characteristics of ca lcium transients and is involved in modulation of synaptic transmission. In our experiments, expression of PV in the lumbar dorsal horn spinal cord was evaluated using densitometric analysis of immunohistological sections and Western-blot techniques in control and arthritic rats. There wa s a significant reduction of PV immunoreactivity in the superficial dorsal horn region ipsilateral to the arthritis after induction of the peripheral inflammation. The ipsilateral area and intensity of PV staining in this area were reduced to 38 % and 37 %, respectively, out of the total PV staining on both sides. It is suggested that this reduction may reflect decreased expression of PV in GABAergic inhibitory neurons. Reduction of PV concentration in the presynaptic GABAergic terminals could lead to potentiation of inhibitory transmission in the spinal cord. Our results suggest that changes in expression of calcium-binding proteins in spinal cord dorsal horn neurons may modulate nociceptive transmission., G. Zachařová, D. Sojka, J. Paleček., and Obsahuje bibliografii
Inhibitory neurotransmission plays a substantial role in encoding of auditory cues relevant for so und localization in vertebrates. While the anatomical organization of the respective afferent auditory brainstem circuits shows remarkable similarities between mammals and birds, the properties of inhibitory neurotransmission in these neural circuits are strikingly different. In mammals, inhibition is predom inantly glyciner gic and endowed with fast kinetics. In birds, inhibition is mediated by γ - Aminobutiric acid (GABA) and too slow to convey temporal information. A further prominent difference lies in the mechanism of inhibition in the respective systems. In auditory brainstem neurons of mammals, [Cl-] i undergoes a developmental shift causing the actions of GABA and glycine to gradually change from depolarization to the ‘classic’ hyperpolarizing-inhibition before hearing onset. Contrary to this, in the mature avian auditory brainstem Cl - homeostasis mechanisms accurately adjust the Cl - gradient to enable depolarizing, but still very efficient, shunting inhibition. The present review considers the mechanisms underlying development of the Cl - homeostasis in the auditory system of mammals and birds and discusses some open issues that require closer attention in future studies., I. Milenković, R. Rübsamen., and Obsahuje bibliografii a bibliografické odkazy
The effects of acute and chronic application of ketamine on the resting spontaneous motility, its development and reactivity was studied in chick embiyos of white Leghorns. 1. Acute application of ketamine (NarcamonR) in a dose of 12.5 mg/kg e.w. partialy depressed spontaneous motility as early as in 11-day old chick embryos . From day 15 of incubation ketamine very effectively blocked spontaneous motility. 2. Ketamine was fully ineffective in spinal preparations (decapitation on day 2 of incubation)of 11- and 13-day-old embryos. It was not until day 15 evoked that it depressed motility as in normal embryos. 3. Chronic continuous supply of ketamine (average dose 6.34 ±0.72 mg/kg e.w./24 h) from day 4 of incubation till day 8, 12, or 16 of incubation reduced the developmental decrease of spontaneous motility by 23.1-6.0 % as compared to the controls. This effect was already observed after the first 4 days of chronic application of ketamine. 4. Chronic application of ketamine significantly diminished the strychnine activation and GABA-mediated depression of spontaneous motility. The depressive effect of the acute application of ketamine itself was hardly affected. The results have shown that ketamine interferes with the development of the endogenous rhythm of intrinsic activity and with the development of reactivity of the generator of embryonic spontaneous motility.
Experimental studies have shown a symmetry-to-asymmetry transition of the spike-timing dependent plasticity (STDP) curve exists in the proximal stratum radiatum (SR) dendrite of the hippocampal CA1 pyramidal neuron, which is probably due to the presence of GABAergic inhibition [2, 3, 4]. A recent computational model predicted that symmetry-to-asymmetry transition is strongly dependent on the frequency and conductance value of GABA inhibition and that the largest long term potentiation (LTP) value and the two distinct long-term depression (LTD) tails of the symmetrical STDP curve are centred at +10 ms, +40 ms and -10 ms, respectively [8, 9]. In the present paper, we continue to investigate even further via computer simulations the effects of gamma frequency inhibition and its conductance value to the symmetry-to-asymmetry transition of the STDP profile in the SR dendrite and predict that the transition is even more robust when there is a temporal offset between the onsets of the pre-post excitatory stimulation and the GABAergic inhibition. The largest LTP value and the two distinct LTD tails are inversely proportional to the increase of GABA conductance.
Epileptic afterdischarges (ADs) elicited by electrical stimulation of sensorimotor cortical area were used as a model to study the role of neurotransmitter systems in cortical seizures in three age groups of developing rats. Drugs augmenting inhibition mediated by GABAA receptors were found to suppress ADs in all age groups, their activity was usually more marked in younger than in 25-day-old rat pups. Drugs potentiating GABAB receptors exhibit lower efficacy and more complicated developmental profile than GABAA-ergic drugs. Effects of an antagonist of GABAB receptor – marked prolongation of ADs in all three age groups – suggest an important role of GABAB receptors in arrest of cortical seizures. Drugs affecting glutamate receptors exhibit variable effects, usually better expressed in older animals than in 12-day-old ones. No specific role for ionotropic as well as metabotropic glutamate receptors could be predicted. Activation of adenosinergic inhibitory modulatory system also exhibited anticonvulsant action in the present model. All three neurotransmitter systems probably participate in mechanisms of generation, maintenance and arrest of cortical seizures., P. Mareš, H. Kubová., and Obsahuje bibliografii a bibliografické odkazy