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Electrophysiological description of mechanisms determining synaptic transmission and its modulation

100%
Mozrzymas J. W.
Acta Neurobiologiae Experimentalis
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2008
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vol. 68
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issue 2
256-263
EN
Signal integration in neurons is a complex process that depends on e.g. the kinetics of synaptic currents, distribution of synaptic connections as well as passive and excitatory membrane properties. The time course of synaptic currents is largely determined by the kinetics of the postsynaptic receptors and the time course of synaptic neurotransmitter concentration. The analysis of current responses to rapid agonist applications provides the means to study the ligand-gated receptor gating but experimentally based estimation of neurotransmitter transient at central synapses was an important challenge during the last decade. Both theoretical as well as experimentally based approaches indicated that synaptic agonist transient is very brief, implying that the activation of postsynaptic receptors occurs in conditions of extreme non-equilibrium. Such a dynamic pattern of activation of postsynaptic receptors has a crucial impact not only on the kinetics of synaptic currents but also on their susceptibility to pharmacological modulation.
2

Electrophysiological description of synaptic transmission and its modulation by pharmacological factors

100%
Mozrzymas J. W.
Postępy Higieny i Medycyny Doświadczalnej
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2000
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vol. 54
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issue 3
403-416
EN
Synaptic transmission between neurons plays a key role in signal transduction in the central nervous system (CNS). Postsynaptic currents can be routinely recorded using the patch-clamp technique but mechanisms underlying their kinetics are not entirely clear. Model simulations and experimental evidence indicate that the time course of synaptic agonist is extremely fast and short lasting implying that activation of postsynaptic receptors takes place in conditions of extreme non-equilibrium. For this reason, studies of postsynaptic receptors? kinetics requires ultrafast agonist application techniques able to mimic synaptic conditions, the goal that only recently has been technically achieved. In the present paper, examples of kinetic studies of synaptic currents and current responses to ultrafast agonist applications are presented. Examples are given that pharmacological modulation of synaptic receptors strongly depends on the non-equilibrium conditions of receptors? activation. Application of kinetic studies to determine subtypes of synaptic receptors are also presented and discussed.
3

The effect of changes in extracellular pH on neuronal GABAA receptors

51%
Zarnowska E. D., Mercik K., Mandat M., Mozrzymas J. W.
Postępy Higieny i Medycyny Doświadczalnej
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2002
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vol. 56
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issue 3
293-305
EN
Local pH values of both intra- and extracellular liquids can be regulated by a number of mechanisms including membrane transport and metabolism. It is known that the changes of extracellular pH accompanying physiological and pathological processes are sufficient to affect several important structures such as ionic channels, transporters, receptors etc. In particular, several reports indicate that GABAA receptor is strongly modulated by this factor. The effect of pH application of ultrafast perfusion system allowed to explore the mechanisms of pH effect on GABAA receptors in neurons. It is concluded that changes in pH exert their effects by allosteric modulation of GABAA receptors.
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