Papers by Meron Gurkiewicz
Frontiers in Neuroinformatics, 2009
Neural Plasticity, 2007
The Israel Society for Neuroscience—ISFN—was founded in 1993 by a group of Israeli leading scient... more The Israel Society for Neuroscience—ISFN—was founded in 1993 by a group of Israeli leading scientists conducting research in the area of neurobiology. The primary goal of the society was to promote and disseminate the knowledge and understanding acquired by its members, and to strengthen interactions between them. Since then, the society holds its annual meeting every year in Eilat usually during December. At this annual meetings, the senior Israeli neurobiologists, their teams, and their graduate students, as well as foreign scientists and students, present their recent research findings in platform and poster presentations, and the program of the meeting is mainly based on the 338 received abstracts which are published in this volume. The meeting also offers the opportunity for the researchers to exchange information with each other, often leading to the initiation of collaborative studies. Both the number of members of the society and those participating in the annual meeting is ...
• Sodium currents were measured from L5 pyramidal neurons using six stimulation protocols in the ... more • Sodium currents were measured from L5 pyramidal neurons using six stimulation protocols in the nucleated and outside-out configurations of the patch-clamp technique and fit to several kinetic models of voltage-gated sodium channels. • Out of a dozen voltage-gated sodium channel (VGSC) models (only relevant configurations shown) it appears that the most simplified, a four-state-16-parameter, Hidden-Markov-Model (HMM) provides the best fit for the data. • The ability of the chosen HMM model to simulate generation and propagation of action potentials (APs) in L5 pyramidal neurons was tested relative to the most prevalent and complete model of morphological influence on firing pattern. • The combination of the simplified HMM and a Hodgkin-Huxley-like voltage-gated potassium channel model provides the best simile of high frequency bursts of APs in L5 pyramidal neurons. • Further development and investigation of an adequate voltage-gated potassium channel HMM is needed to replace the HH paradigm.
PLoS Comput Biol, Jan 1, 2007
The activity of trans-membrane proteins such as ion channels is the essence of neuronal transmiss... more The activity of trans-membrane proteins such as ion channels is the essence of neuronal transmission. The currently most accurate method for determining ion channel kinetic mechanisms is single-channel recording and analysis. Yet, the limitations and complexities in interpreting single-channel recordings discourage many physiologists from using them. Here we show that a genetic search algorithm in combination with a gradient descent algorithm can be used to fit whole-cell voltage-clamp data to kinetic models with a high degree of accuracy. Previously, ion channel stimulation traces were analyzed one at a time, the results of these analyses being combined to produce a picture of channel kinetics. Here the entire set of traces from all stimulation protocols are analysed simultaneously. The algorithm was initially tested on simulated current traces produced by several Hodgkin-Huxley–like and Markov chain models of voltage-gated potassium and sodium channels. Currents were also produced by simulating levels of noise expected from actual patch recordings. Finally, the algorithm was used for finding the kinetic parameters of several voltage-gated sodium and potassium channels models by matching its results to data recorded from layer 5 pyramidal neurons of the rat cortex in the nucleated outside-out patch configuration. The minimization scheme gives electrophysiologists a tool for reproducing and simulating voltage-gated ion channel kinetics at the cellular level.
Journal of …, Jan 1, 2011
Gain-of-function mutations of the voltage-gated sodium channel (VGSC) Nav1.7 have been linked to ... more Gain-of-function mutations of the voltage-gated sodium channel (VGSC) Nav1.7 have been linked to human pain disorders. The mutation F1449V, located at the intracellular end of transmembrane helix S6 of domain III, induces the inherited pain syndrome erythromelalgia. A kinetic model of wild-type (WT) and F1449V Nav1.7 may provide a basis for predicting putative intra-protein interactions. Here, we semi-automatically constrained a Markov model using stochastic search algorithms and whole-cell patch-clamp recordings from HEK cells transfected with Nav1.7 and its F1449V mutation. The best models obtained simulated known differences in action potential thresholds and firing patterns in spinal sensory neurons expressing WT and F1449V. The most suitable Markov model consisted of three closed, one open and two inactivated states. The model predicted that the F1449V mutation shifts occupancy of the closed states closer to the open state, making it easier for the channel pore to open. It also predicted that F1449V's second inactivated state is more than four times more likely to be occupied than the equivalent state in WT at hyperpolarized potentials, even though the mutation still lowered the firing threshold of action potentials. The differences between WT and F1449V were not limited to a single transition. Thus, a point mutation in position F1449, while phenotypically most probably affecting the activation gate, may also modify channel functions mediated by structures in more distant areas of the channel protein.
Pflügers Archiv European Journal of …, Jan 1, 2006
Ever since the publication of the Hamill et al.
[Hamill et al., Pflügers Arch, 391:85–100, 1981] ... more Ever since the publication of the Hamill et al.
[Hamill et al., Pflügers Arch, 391:85–100, 1981] paper and
the following increase in popularity of acute brain slice
preparations, there has been a large increase in the volume
of publications investigating voltage-gated channels in the
central nervous system using the patch-clamp technique. In
the preceding decade, investigations of voltage-gated
channels have moved out of the somatic region into
dendrites providing much needed information about dendritic
voltage-gated channels. In this study, we review
some aspects related to the investigation of voltage-gated
ion channels in dendrites: recording, analysis, and function.
Frontiers in …, Jan 1, 2009
Science, Jan 1, 2009
THE VENEZUELAN ACADEMY OF PHYSICAL, MATHEMATICAL, AND NATURAL SCIENCES WOULD like to share with t... more THE VENEZUELAN ACADEMY OF PHYSICAL, MATHEMATICAL, AND NATURAL SCIENCES WOULD like to share with the international scientific community our fears for the present and future fate of science and higher education in our country. A number of worrisome recent ...
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Papers by Meron Gurkiewicz
[Hamill et al., Pflügers Arch, 391:85–100, 1981] paper and
the following increase in popularity of acute brain slice
preparations, there has been a large increase in the volume
of publications investigating voltage-gated channels in the
central nervous system using the patch-clamp technique. In
the preceding decade, investigations of voltage-gated
channels have moved out of the somatic region into
dendrites providing much needed information about dendritic
voltage-gated channels. In this study, we review
some aspects related to the investigation of voltage-gated
ion channels in dendrites: recording, analysis, and function.
[Hamill et al., Pflügers Arch, 391:85–100, 1981] paper and
the following increase in popularity of acute brain slice
preparations, there has been a large increase in the volume
of publications investigating voltage-gated channels in the
central nervous system using the patch-clamp technique. In
the preceding decade, investigations of voltage-gated
channels have moved out of the somatic region into
dendrites providing much needed information about dendritic
voltage-gated channels. In this study, we review
some aspects related to the investigation of voltage-gated
ion channels in dendrites: recording, analysis, and function.