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Johansson, Staffan
Publications (10 of 21) Show all publications
Yelhekar, T. D., Druzin, M. & Johansson, S. (2017). Contribution of Resting Conductance, GABA(A)-Receptor Mediated Miniature Synaptic Currents and Neurosteroid to Chloride Homeostasis in Central Neurons. eNeuro, 4(2), Article ID e0019.
Open this publication in new window or tab >>Contribution of Resting Conductance, GABA(A)-Receptor Mediated Miniature Synaptic Currents and Neurosteroid to Chloride Homeostasis in Central Neurons
2017 (English)In: eNeuro, ISSN 2373-2822, Vol. 4, no 2, article id e0019Article in journal (Refereed) Published
Abstract [en]

Maintenance of a low intraneuronal Cl- concentration, [Cl-](i), is critical for inhibition in the CNS. Here, the contribution of passive, conductive Cl- flux to recovery of [Cl-](i) after a high load was analyzed in mature central neurons from rat. A novel method for quantifying the resting Cl- conductance, important for [Cl-](i) recovery, was developed and the possible contribution of GABAA and glycine receptors and of ClC-2 channels to this conductance was analyzed. The hypothesis that spontaneous, action potential-independent release of GABA is important for [Cl-](i) recovery was tested. [Cl-](i) was examined by gramicidin-perforated patch recordings in medial preoptic neurons. Cells were loaded with Cl- by combining GABA or glycine application with a depolarized voltage, and the time course of [Cl-](i) was followed by measurements of the Cl- equilibrium potential, as obtained from the current recorded during voltage ramps combined with GABA or glycine application. The results show that passive Cl- flux contributes significantly, in the same order of magnitude as does K+-Cl- cotransporter 2 (KCC2), to [Cl-](i) recovery and that Cl- conductance accounts for similar to 6% of the total resting conductance. A major fraction of this resting Cl- conductance is picrotoxin (PTX)-sensitive and likely due to open GABAA receptors, but ClC-2 channels do not contribute. The results also show that when the decay of GABAA receptor-mediated miniature postsynaptic currents (minis) is slowed by the neurosteroid allopregnanolone, such minis may significantly quicken [Cl-](i) recovery, suggesting a possible steroid-regulated role for minis in the control of Clhomeostasis.

Keywords
chloride homeostasis, GABA(A) receptor, KCC2, miniature postsynaptic current, neurosteroid, resting loride conductance
National Category
Physiology
Identifiers
urn:nbn:se:umu:diva-133788 (URN)10.1523/ENEURO.0019-17.2017 (DOI)000397567900003 ()
Note

Originally published in manuscript form

Available from: 2017-04-24 Created: 2017-04-24 Last updated: 2018-06-09Bibliographically approved
Druzin, M. & Johansson, S. (2016). 2-Aminoethyl Diphenylborinate Blocks GABAA-Receptor-Mediated Currents in Rat Medial Preoptic Neurons. Opera Medica Et Physiologica, 2(1), 63-68
Open this publication in new window or tab >>2-Aminoethyl Diphenylborinate Blocks GABAA-Receptor-Mediated Currents in Rat Medial Preoptic Neurons
2016 (English)In: Opera Medica Et Physiologica, ISSN 2500-2295, Vol. 2, no 1, p. 63-68Article in journal (Refereed) Published
Abstract [en]

The effect of 2-aminoethyl diphenylborinate (2-APB), a commonly used drug to modulate inositol-1,4,5-triphosphate (IP3) receptors and transient receptor potential (TRP) channels, on GABAA receptor-mediatedcurrents was studied in neurons from the medial preoptic nucleus (MPN) of rat. 2-APB gradually and reversibly reducedthe currents evoked by GABA but had no effect on the currents evoked by glycine. The blocking effect was not mediatedby alterations in intracellular calcium concentration and showed a concentration dependence with half maximal effect at~50 μM 2-APB, for currents evoked by 100 μM, as well as by 1.0 mM GABA, suggesting that 2-APB is not competing withGABA for its binding site at the GABAA receptor. Thus, the present study describes a novel pharmacological property of2-APB as a non-competitive blocker of GABAA receptors and calls for caution in the interpretation of the results where2-APB is used to affect IP3 receptors or TRP channels.

Place, publisher, year, edition, pages
Lobachevsky State University of Nizhny Novgorod, 2016
National Category
Physiology
Identifiers
urn:nbn:se:umu:diva-133366 (URN)20388/OMP2016.001.0021 (DOI)
Available from: 2017-04-07 Created: 2017-04-07 Last updated: 2018-06-09Bibliographically approved
Johansson, S., Yelhekar, T. D. & Druzin, M. (2016). Commentary: Chloride Regulation: a Dynamic Equilibrium Crucial for Synaptic Inhibition. Frontiers in Cellular Neuroscience, 10, Article ID 182.
Open this publication in new window or tab >>Commentary: Chloride Regulation: a Dynamic Equilibrium Crucial for Synaptic Inhibition
2016 (English)In: Frontiers in Cellular Neuroscience, ISSN 1662-5102, E-ISSN 1662-5102, Vol. 10, article id 182Article in journal, Editorial material (Refereed) Published
Keywords
Cl- channel, K+ Cl- cotransporter 2, conductance, membrane potential, synaptic inhibition, Cl concentration, equilibrium potential
National Category
Neurosciences Physiology
Identifiers
urn:nbn:se:umu:diva-127569 (URN)10.3389/fncel.2016.00182 (DOI)000379894400002 ()27487962 (PubMedID)
Available from: 2016-11-16 Created: 2016-11-16 Last updated: 2018-06-09Bibliographically approved
Yelhekar, T. D., Druzin, M., Karlsson, U., Blomqvist, E. & Johansson, S. (2016). How to Properly Measure a Current-Voltage Relation? -Interpolation vs. Ramp Methods Applied to Studies of GABA(A) Receptors. Frontiers in Cellular Neuroscience, 10, Article ID 10.
Open this publication in new window or tab >>How to Properly Measure a Current-Voltage Relation? -Interpolation vs. Ramp Methods Applied to Studies of GABA(A) Receptors
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2016 (English)In: Frontiers in Cellular Neuroscience, ISSN 1662-5102, E-ISSN 1662-5102, Vol. 10, article id 10Article in journal (Refereed) Published
Abstract [en]

The relation between current and voltage, I-V relation, is central to functional analysis of membrane ion channels. A commonly used method, since the introduction of the voltage-clamp technique, to establish the I-V relation depends on the interpolation of current amplitudes recorded at different steady voltages. By a theoretical computational approach as well as by experimental recordings from GABA(A) receptor mediated currents in mammalian central neurons, we here show that this interpolation method may give reversal potentials and conductances that do not reflect the properties of the channels studied under conditions when ion flux may give rise to concentration changes. Therefore, changes in ion concentrations may remain undetected and conclusions on changes in conductance, such as during desensitization, may be mistaken. In contrast, an alternative experimental approach, using rapid voltage ramps, enable I-V relations that much better reflect the properties of the studied ion channels.

Keywords
current-voltage relation, voltage clamp, reversal potential, conductance, concentration changes, interpolation, voltage ramp, ion channel
National Category
Physiology Neurosciences
Identifiers
urn:nbn:se:umu:diva-127570 (URN)10.3389/fncel.2016.00010 (DOI)000369141200001 ()26869882 (PubMedID)
Available from: 2016-11-16 Created: 2016-11-16 Last updated: 2018-06-09Bibliographically approved
Chizhov, A. V., Malinina, E., Druzin, M., Graham, L. J. & Johansson, S. (2014). Firing clamp: a novel method for single-trial estimation of excitatory and inhibitory synaptic neuronal conductances.. Frontiers in cellular neuroscience, 8(86), 86
Open this publication in new window or tab >>Firing clamp: a novel method for single-trial estimation of excitatory and inhibitory synaptic neuronal conductances.
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2014 (English)In: Frontiers in cellular neuroscience, ISSN 1662-5102, Vol. 8, no 86, p. 86-Article in journal (Refereed) Published
Abstract [en]

Understanding non-stationary neuronal activity as seen in vivo requires estimation of both excitatory and inhibitory synaptic conductances from a single trial of recording. For this purpose, we propose a new intracellular recording method, called "firing clamp." Synaptic conductances are estimated from the characteristics of artificially evoked probe spikes, namely the spike amplitude and the mean subthreshold potential, which are sensitive to both excitatory and inhibitory synaptic input signals. The probe spikes, timed at a fixed rate, are evoked in the dynamic-clamp mode by injected meander-like current steps, with the step duration depending on neuronal membrane voltage. We test the method with perforated-patch recordings from isolated cells stimulated by external application or synaptic release of transmitter, and validate the method with simulations of a biophysically-detailed neuron model. The results are compared with the conductance estimates based on conventional current-clamp recordings.

Keywords
synaptic conductance estimation, dynamic clamp, firing-clamp
National Category
Physiology
Identifiers
urn:nbn:se:umu:diva-88025 (URN)10.3389/fncel.2014.00086 (DOI)000333416900001 ()24734000 (PubMedID)
Available from: 2014-04-22 Created: 2014-04-22 Last updated: 2018-06-08Bibliographically approved
Karlsson, U., Druzin, M. & Johansson, S. (2011). Cl− concentration changes and desensitization of GABAA and glycine receptors. The Journal of General Physiology, 138(6), 609-626
Open this publication in new window or tab >>Cl concentration changes and desensitization of GABAA and glycine receptors
2011 (English)In: The Journal of General Physiology, ISSN 0022-1295, E-ISSN 1540-7748, Vol. 138, no 6, p. 609-626Article in journal (Refereed) Published
Abstract [en]

Desensitization of ligand-gated ion channels plays a critical role for the information transfer between neurons. The current view on γ-aminobutyric acid (GABA)A and glycine receptors includes significant rapid components of desensitization as well as cross-desensitization between the two receptor types. Here, we analyze the mechanism of apparent cross-desensitization between native GABAA and glycine receptors in rat central neurons and quantify to what extent the current decay in the presence of ligand is a result of desensitization versus changes in intracellular Cl concentration ([Cl]i). We show that apparent cross-desensitization of currents evoked by GABA and by glycine is caused by changes in [Cl]i. We also show that changes in [Cl]i are critical for the decay of current in the presence of either GABA or glycine, whereas changes in conductance often play a minor role only. Thus, the currents decayed significantly quicker than the conductances, which decayed with time constants of several seconds and in some cells did not decay below the value at peak current during 20-s agonist application. By taking the cytosolic volume into account and numerically computing the membrane currents and expected changes in [Cl]i, we provide a theoretical framework for the observed effects. Modeling diffusional exchange of Cl between cytosol and patch pipettes, we also show that considerable changes in [Cl]i may be expected and cause rapidly decaying current components in conventional whole cell or outside-out patch recordings. The findings imply that a reevaluation of the desensitization properties of GABAA and glycine receptors is needed.

National Category
Physiology
Identifiers
urn:nbn:se:umu:diva-2614 (URN)10.1085/jgp.201110674 (DOI)
Available from: 2007-10-04 Created: 2007-10-04 Last updated: 2018-06-09Bibliographically approved
Druzin, M., Malinina, E., Grimsholm, O. & Johansson, S. (2011). Mechanism of estradiol-induced block of voltage-gated K+ currents in rat medial preoptic neurons.. PLoS ONE, 6(5), e20213
Open this publication in new window or tab >>Mechanism of estradiol-induced block of voltage-gated K+ currents in rat medial preoptic neurons.
2011 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 6, no 5, p. e20213-Article in journal (Refereed) Published
Abstract [en]

The present study was conducted to characterize possible rapid effects of 17-β-estradiol on voltage-gated K(+) channels in preoptic neurons and, in particular, to identify the mechanisms by which 17-β-estradiol affects the K(+) channels. Whole-cell currents from dissociated rat preoptic neurons were studied by perforated-patch recording. 17-β-Estradiol rapidly (within seconds) and reversibly reduced the K(+) currents, showing an EC(50) value of 9.7 µM. The effect was slightly voltage dependent, but independent of external Ca(2+), and not sensitive to an estrogen-receptor blocker. Although 17-α-estradiol also significantly reduced the K(+) currents, membrane-impermeant forms of estradiol did not reduce the K(+) currents and other estrogens, testosterone and cholesterol were considerably less effective. The reduction induced by estradiol was overlapping with that of the K(V)-2-channel blocker r-stromatoxin-1. The time course of K(+) current in 17-β-estradiol, with a time-dependent inhibition and a slight dependence on external K(+), suggested an open-channel block mechanism. The properties of block were predicted from a computational model where 17-β-estradiol binds to open K(+) channels. It was concluded that 17-β-estradiol rapidly reduces voltage-gated K(+) currents in a way consistent with an open-channel block mechanism. This suggests a new mechanism for steroid action on ion channels.

Place, publisher, year, edition, pages
San Francisco: Public Library of Science, 2011
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:umu:diva-53900 (URN)10.1371/journal.pone.0020213 (DOI)21625454 (PubMedID)
Available from: 2012-04-04 Created: 2012-04-04 Last updated: 2018-06-08Bibliographically approved
Malinina, E., Druzin, M. & Johansson, S. (2010). Differential control of spontaneous and evoked GABA release by presynaptic L-type Ca(2+) channels in the rat medial preoptic nucleus. Journal of Neurophysiology, 104(1), 200-209
Open this publication in new window or tab >>Differential control of spontaneous and evoked GABA release by presynaptic L-type Ca(2+) channels in the rat medial preoptic nucleus
2010 (English)In: Journal of Neurophysiology, ISSN 0022-3077, E-ISSN 1522-1598, Vol. 104, no 1, p. 200-209Article in journal (Refereed) Published
Abstract [en]

To clarify the role of presynaptic L-type Ca(2+) channels in GABA-mediated transmission in the medial preoptic nucleus (MPN), spontaneous, miniature, and impulse-evoked inhibitory postsynaptic currents (sIPSCs, mIPSCs, and eIPSCs, respectively) were recorded from MPN neurons in a slice preparation from rat brain. The effects of different stimulus protocols and pharmacological tools to detect contributions of L-type Ca(2+) channels and of Ca(2+)-activated K(+) (K(Ca)) channels were analyzed. Block of L-type channels did not affect the sIPSC and mIPSC properties (frequency, amplitude, decay time course) in the absence of external stimulation but unexpectedly potentiated the eIPSCs evoked at low stimulus frequency (0.1-2.0 Hz). This effect was similar to and overlapping with the effect of K(Ca)-channel blockers. High-frequency stimulation (50 Hz for 10 s) induced a substantial posttetanic potentiation (PTP) of the eIPSC amplitude and of the sIPSC frequency. Block of L-type channels still potentiated the eIPSC during PTP, but in contrast, reduced the sIPSC frequency during PTP. It was concluded that L-type channels provide a means for differential control of spontaneous and impulse-evoked GABA release and that this differential control is prominent during short-term synaptic plasticity. Functional coupling of the presynaptic L-type channels to K(Ca) channels explains the observed effects on eIPSCs.

National Category
Neurosciences
Identifiers
urn:nbn:se:umu:diva-42241 (URN)10.1152/jn.00570.2009 (DOI)000279586400018 ()20463198 (PubMedID)
Available from: 2011-04-06 Created: 2011-04-06 Last updated: 2018-06-08Bibliographically approved
Klement, G., Druzin, M., Haage, D., Malinina, E., Århem, P. & Johansson, S. (2010). Spontaneous ryanodine-receptor-dependent Ca2+-activated K+ currents and hyperpolarizations in rat medial preoptic neurons. Journal of Neurophysiology, 103(5), 2900-2911
Open this publication in new window or tab >>Spontaneous ryanodine-receptor-dependent Ca2+-activated K+ currents and hyperpolarizations in rat medial preoptic neurons
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2010 (English)In: Journal of Neurophysiology, ISSN 0022-3077, E-ISSN 1522-1598, Vol. 103, no 5, p. 2900-2911Article in journal (Refereed) Published
Abstract [en]

The aim of the present study was to clarify the identity of slow spontaneous currents, the underlying mechanism and possible role for impulse generation in neurons of the rat medial preoptic nucleus (MPN). Acutely dissociated neurons were studied with the perforated patch-clamp technique. Spontaneous outward currents, at a frequency of approximately 0.5 Hz and with a decay time constant of approximately 200 ms, were frequently detected in neurons when voltage-clamped between approximately -70 and -30 mV. The dependence on extracellular K(+) concentration was consistent with K(+) as the main charge carrier. We concluded that the main characteristics were similar to those of spontaneous miniature outward currents (SMOCs), previously reported mainly for muscle fibers and peripheral nerve. From the dependence on voltage and from a pharmacological analysis, we concluded that the currents were carried through small-conductance Ca(2+)-activated (SK) channels, of the SK3 subtype. From experiments with ryanodine, xestospongin C, and caffeine, we concluded that the spontaneous currents were triggered by Ca(2+) release from intracellular stores via ryanodine receptor channels. An apparent voltage dependence was explained by masking of the spontaneous currents as a consequence of steady SK-channel activation at membrane potentials > -30 mV. Under current-clamp conditions, corresponding transient hyperpolarizations occasionally exceeded 10 mV in amplitude and reduced the frequency of spontaneous impulses. In conclusion, MPN neurons display spontaneous hyperpolarizations triggered by Ca(2+) release via ryanodine receptors and SK3-channel activation. Thus such events may affect impulse firing of MPN neurons.

National Category
Physiology
Identifiers
urn:nbn:se:umu:diva-41336 (URN)10.1152/jn.00566.2009 (DOI)000277564500051 ()20457857 (PubMedID)
Available from: 2011-03-23 Created: 2011-03-23 Last updated: 2018-06-08Bibliographically approved
Malinina, E., Druzin, M. & Johansson, S. (2006). Short-term plasticity in excitatory synapses of the rat medial preoptic nucleus.. Brain Research, 1110(1), 128-35
Open this publication in new window or tab >>Short-term plasticity in excitatory synapses of the rat medial preoptic nucleus.
2006 (English)In: Brain Research, ISSN 0006-8993, Vol. 1110, no 1, p. 128-35Article in journal (Refereed) Published
Abstract [en]

The medial preoptic nucleus (MPN) regulates sexual behavior which is subject to experience-dependent modifications. Such modifications must depend on functional plasticity in the controlling neural circuits. Thus, MPN synapses are likely candidates for the site of alterations. The present work is a first systematic study of functional synaptic plasticity at glutamatergic synapses in the MPN. Short-term activity-dependent plasticity was investigated using a slice preparation from young male rats. The average efficacy of AMPA/kainate-receptor-mediated synaptic transmission was activity-dependent, showing a peak at a steady stimulation rate of 2 Hz. The variation in efficacy was attributed to mainly presynaptic factors since the average response amplitude was roughly paralleled by the response probability. Upon paired-pulse stimulation, paired-pulse facilitation as well as paired-pulse depression was observed. In some cases, paired-pulse facilitation as well as paired-pulse depression was recorded from an individual neuron depending on the interval between the paired stimuli. On average, paired-pulse facilitation was observed at intervals <500 ms, and paired-pulse depression at intervals in the range 1-4 s. The findings thus reveal complex activity-dependent short-term plasticity of the functional synaptic properties in the medial preoptic nucleus.

Keywords
Animals, Dose-Response Relationship; Radiation, Electric Stimulation/methods, Excitatory Postsynaptic Potentials/*physiology/radiation effects, Neuronal Plasticity/*physiology, Preoptic Area/*cytology, Rats, Rats; Sprague-Dawley, Synapses/*physiology, Time Factors
Identifiers
urn:nbn:se:umu:diva-12593 (URN)doi:10.1016/j.brainres.2006.06.061 (DOI)16870159 (PubMedID)
Available from: 2008-01-11 Created: 2008-01-11 Last updated: 2018-06-09Bibliographically approved
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