Search

Start Over Creator Vyklický, L.

2. Activation and Modulation of Ligand-Gated Ion Channels

Creator:
Krůšek, J., Dittert, I., Hendrych, T., Hník, P., Horák, M., Petrovic, M., Sedláček, M., Sušánková, K., Svobodová, L., Toušová, K., Ujec, E., Vlachová, V., Vyklický, L., Vyskočil, F., and Vyklický jr., L.
Type:
article, model:article, and TEXT
Subject:
Acetylcholine receptor, GABA receptor, gluatmate receptor, NMDA receptor, Vanilloid receptor, TRP receptor, and Ionic channel
Language:
English
Description:
Ligand-gated ionic channels are integral membrane proteins that enable rapid and selective ion fluxes across biological membranes. In excitable cells, their role is crucial for generation and propagation of electrical signals. This survey describes recent results from studies performed in the Department of Cellular Neurophysiology, Institute of Physiology ASCR, aimed at exploring the conformational dynamics of the acetylcholine, glutamate and vanilloid receptors during their activation, inactivation and desensitization. Distinct families of ion channels were selected to illustrate a rich complexity of the functional states and conformational transitions these proteins undergo. Particular attention is focused on structure-function studies and allosteric modulation of their activity. Comprehension of the fundamental principles of mechanisms involved in the operation of ligand-gated ion channels at the cellular and molecular level is an essential prerequisite for gaining an insight into the pathogenesis of many psychiatric and neurological disorders and for efficient development of novel specifically targeted drugs.
Rights:
http://creativecommons.org/licenses/by-nc-sa/4.0/ and policy:public

3. Can sensory neurones in culture serve as a model of nociception?

Creator:
Vyklický, L. and Knotková-urbancová, H.
Type:
article, model:article, and TEXT
Subject:
sensory neurones, short-term culture, nociception, membrane currents, and algogens
Language:
English
Description:
Nociceptors belong to Ad and C afferents that are equipped in the periphery with receptors for detecting potentially damaging physical and chemical stimuli. This review summarizes experimental evidence that these receptors represented by ionic channels are also functionally expressed on the cell bodies of sensory neurones in short-term cultures. The nociceptors belong predominantly to the small and medium size DRG neurones in which algogens such as weak acids, capsaicin, bradykinin and serotonin produce inward currents that can generate impulse activity. It seems likely that the neurones which are not sensitive to algogens but to GABA, ATP or glutamate, agents not producing pain in humans, belong to other categories of DRG neurones equipped for detecting other modalities of sensation. New techniques for physical stimulation of DRG neurones in culture may be of great help in the search for complementing the criteria for distinguishing nociceptors among other neurones in culture. It is suggested that such an in vitro model will be useful for studying cellular mechanisms of nociception.
Rights:
http://creativecommons.org/licenses/by-nc-sa/4.0/ and policy:public

4. Capsaicin-induced membrane currents in cultured sensory neurons of the rat

Creator:
Vlachová, V. and Vyklický, L.
Type:
article, model:article, and TEXT
Subject:
sensory neurons, rat, capsaicin, GABA, membrane currents, and primary culture
Language:
English
Description:
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.
Rights:
http://creativecommons.org/licenses/by-nc-sa/4.0/ and policy:public

5. GABAa membrane currents are insensitive to extracellular acidification in cultured sensory neurons of the frog

Creator:
Vyklický, L., Philippi, M., Kuffler, D. P., and Orkand, R. K.
Type:
article, model:article, and TEXT
Subject:
sensory neurons, short term culture, frog, GABAa receptors, and pH
Language:
English
Description:
The effects of decreasing extracellular pH from 7.4 to 6.0 or 5.8 on whole cell membrane currents induced by GABA (10-100 //M) were studied in dorsal root ganglion (DRG) neurons of the frog in short-term culture using the whole cell patch-clamp technique. In 45 of 50 cells the GABA currents were the same at both normal and reduced pH. In the remaining 5 cells, acidification increased the response. The reversal potential for the current, about +5 mV, was the same at reduced and normal pH. These results contrast with the effect of the same pH reduction which markedly reduces the current resulting from glutamate activation of receptors on central neurons (Traynelis and Cull-Candy 1990, Vyklicky Jr. et ai 1990, Tang et al. 1990). These findings suggest that acidification under pathophysiological conditions plays a protective role in preventing excessive excitation not only by decreasing glutamate responses but also by leaving the inhibitory GABAa responses intact.
Rights:
http://creativecommons.org/licenses/by-nc-sa/4.0/ and policy:public