Robert Kraft

Publications of Robert Kraft

• Transient receptor potential melastatin 2 is required for lipopolysaccharide-induced cytokine production in human monocytes.

  Authors: Janine Wehrhahn, Robert Kraft, Christian Harteneck, Sunna Hauschildt

  Journal of immunology (Baltimore, Md. : 1950). 03/2010; 184(5):2386-93.

  Transient receptor potential melastatin 2 (TRPM2) is a Ca(2+)-permeable nonselective cation channel that is stimulated by oxidative stress and specifically activated by intracellular ADP-ribose.Transient receptor potential melastatin 2 (TRPM2) is a Ca(2+)-permeable nonselective cation channel that is stimulated by oxidative stress and specifically activated by intracellular ADP-ribose. Because TRPM2 is highly expressed in immunocytes, a role of this channel in inflammation processes has been proposed. The aim of the current study was to determine the function of TRPM2 in LPS-induced cytokine production of human monocytes. Incubation of human primary monocytes with LPS resulted in an upregulation of TRPM2 mRNA, protein, and of ADP-ribose-induced membrane currents. By using short hairpin RNA to downregulate TRPM2 expression in THP-1 monocytes, we demonstrate that TRPM2 is required for the LPS-induced production of IL-6, IL-8, IL-10, and TNF-alpha. Application of LPS led to a time-dependent increase in intracellular Ca(2+) concentrations in THP-1 cells that was clearly reduced by downregulation of TRPM2. Omission of extracellular Ca(2+) strongly decreased TNF-alpha production in TRPM2-expressing cells. Thus, TRPM2-mediated Ca(2+) entry is a central mechanism for LPS-induced cytokine production in monocytic cells. The identification of TRPM2 as a major player in this LPS-dependent process makes it a promising tool in modulating monocyte functions.

• TRPM3 is expressed in sphingosine-responsive myelinating oligodendrocytes.

  Authors: Anja Hoffmann, Christian Grimm, Robert Kraft, Olaf Goldbaum, Arne Wrede, Christiane Nolte, Uwe-Karsten Hanisch, Christiane Richter-Landsberg, Wolfgang Brück, Helmut Kettenmann, Christian Harteneck

  Journal of neurochemistry. 02/2010; 114(3):654-65.

  Oligodendrocytes are the myelin-forming cells of the CNS and guarantee proper nerve conduction. Sphingosine, one major component of myelin, has recently been identified to activate TRPM3, a member ofOligodendrocytes are the myelin-forming cells of the CNS and guarantee proper nerve conduction. Sphingosine, one major component of myelin, has recently been identified to activate TRPM3, a member of the melastatin-related subfamily of transient receptor potential (TRP) channels. TRPM3 has been demonstrated to be expressed in brain with unknown cellular distribution. Here, we show for the first time that TRPM3 is expressed in oligodendrocytes in vitro and in vivo. TRPM3 is present during oligodendrocyte differentiation. Immunohistochemistry of adult rat brain slices revealed staining of white matter areas, which co-localized with oligodendrocyte markers. Analysis of the developmental distribution revealed that, prior to myelination, TRPM3 channels are localized on neurons. On oligodendrocytes they are found after the onset of myelination. RT-PCR studies showed that the transcription of TRPM3 splice variants is also developmentally regulated in vitro. Ca(2+) imaging approaches revealed the presence of a sphingosine-induced Ca(2+) entry mechanism in oligodendrocytes - with a pharmacological profile similar to the profile published for heterologously expressed TRPM3. These findings indicate that TRPM3 participates as a Ca(2+)-permeable and sphingosine-activated channel in oligodendrocyte differentiation and CNS myelination.

• The Na+/Ca2+ exchange inhibitor KB-R7943 potently blocks TRPC channels.

  Authors: Robert Kraft

  Biochemical and biophysical research communications. 10/2007; 361(1):230-6.

  Na(+)/Ca(2+) exchangers (NCXs) and members of the canonical transient receptor potential (TRPC) channels play an important role in Ca(2+) homeostasis in heart and brain. With respect to theirNa(+)/Ca(2+) exchangers (NCXs) and members of the canonical transient receptor potential (TRPC) channels play an important role in Ca(2+) homeostasis in heart and brain. With respect to their overlapping expression and their role as physiological Ca(2+) influx pathways a functional discrimination of both mechanisms seems to be necessary. Here, the effect of the reverse-mode NCX inhibitor KB-R7943 was investigated on different TRPC channels heterologously expressed in HEK293 cells. In patch-clamp recordings KB-R7943 potently blocked currents through TRPC3 (IC(50)=0.46 microM), TRPC6 (IC(50)=0.71 microM), and TRPC5 (IC(50)=1.38 microM). 1-Oleoyl-2-acetyl-sn-glycerol-induced Ca(2+) entry was nearly completely suppressed by 10 microM KB-R7943 in TRPC6-transfected cells. Thus, KB-R7943 is able to block receptor-operated TRP channels at concentrations which are equal or below those required to inhibit reverse-mode NCX activity. These data further suggest that the protective effects of KB-R7943 in ischemic tissue may, at least partly, be due to inhibition of TRPC channels.

• N-(p-amylcinnamoyl)anthranilic acid (ACA): a phospholipase A(2) inhibitor and TRP channel blocker.

  Authors: Christian Harteneck, Henning Frenzel, Robert Kraft

  Cardiovascular drug reviews. 02/2007; 25(1):61-75.

  Phospholipase A(2) enzymes display a superfamily of structurally different enzymes classified in at least nine subfamilies by biochemical and structural properties. N-(p-amylcinnamoyl)anthranilicPhospholipase A(2) enzymes display a superfamily of structurally different enzymes classified in at least nine subfamilies by biochemical and structural properties. N-(p-amylcinnamoyl)anthranilic acid commonly referred to as ACA is often used as a broad-spectrum inhibitor for the characterization of phospholipase A(2)-mediated pathways. Compounds like ACA and ACA-like structures have been described to block the receptor-induced release of arachidonic acid and subsequent signaling cascades in the pancreas and the cardiovascular system. We showed that ACA directly blocks several transient receptor potential (TRP) channels (TRPC6, TRPM2, TRP and TRPM8). With respect to the published data of ACA in the phospholipase A(2) field, the finding that ACA blocks diacylglycerol-activated TRP channels is of specific interest as it offers the opportunity to interfere with receptor-induced calcium-dependent signaling processes in platelets and vascular smooth muscle cells. Overall, N-phenylcinnamides, as a new pharmaceutical lead structure, form the first class of synthetic TRP channel blockers and represent a promising start for the development of small organic TRP channel-specific blockers.

• TRPV4-mediated regulation of epithelial permeability.

  Authors: Bettina Reiter, Robert Kraft, Dorothee Günzel, Sebastian Zeissig, Jörg-Dieter Schulzke, Michael Fromm, Christian Harteneck

  The FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 10/2006; 20(11):1802-12.

  TRPV4 is a calcium-permeable channel activated by extracellular hypotonicity, polyunsaturated fatty acids, phorbol esters, and heat. We show that TRPV4 is localized in the basolateral membrane of theTRPV4 is a calcium-permeable channel activated by extracellular hypotonicity, polyunsaturated fatty acids, phorbol esters, and heat. We show that TRPV4 is localized in the basolateral membrane of the mouse mammary cell line HC11. Activation of TRPV4 caused an increase in the intracellular Ca(2+) concentration through influx of extracellular Ca(2+), triggering two independent chains of events: 1) a rapid increase in transcellular conductance through the activation of apical large conductance calcium-activated (BK) potassium channels that were blockable by paxilline; 2) a slow increase in paracellular permeability for small solutes. The latter effect was accompanied by a down-regulation of the tight junctional proteins claudin -1, -3, -4, -5, -7, and -8 and by dramatic changes in tight junction morphology, including frequent large breaks in the tight junction strands. This dual modulation of epithelial permeability after TRPV4 activation may be involved in regulating the tonicity across mammary gland epithelia. TRPV4 activation may also be responsible for exudation and edema formation during inflammation processes.-Reiter, B., Kraft, R., Günzel, D., Zeissig, S., Schulzke, J-D., Fromm, M., Harteneck, C. TRPV4-mediated regulation of epithelial permeability.

• Inhibition of TRPM2 cation channels by N-(p-amylcinnamoyl)anthranilic acid.

  Authors: Robert Kraft, Christian Grimm, Henning Frenzel, Christian Harteneck

  British journal of pharmacology. 07/2006; 148(3):264-73.

  1. TRPM2 is a Ca2+ -permeable nonselective cation channel activated by intracellular ADP-ribose (ADPR) and by hydrogen peroxide (H2O2). We investigated the modulation of TRPM2 activity by1. TRPM2 is a Ca2+ -permeable nonselective cation channel activated by intracellular ADP-ribose (ADPR) and by hydrogen peroxide (H2O2). We investigated the modulation of TRPM2 activity by N-(p-amylcinnamoyl)anthranilic acid (ACA). ACA has previously been reported to inhibit phospholipase A2 (PLA2). 2. Using patch-clamp and calcium-imaging techniques, we show that extracellular application of 20 microM ACA completely blocked ADPR-induced whole-cell currents and H2O2-induced Ca2+ signals (IC50 = 1.7 microM) in HEK293 cells transfected with human TRPM2. Two other PLA2 inhibitors, p-bromophenacyl bromide (BPB; 100 microM) and arachidonyl trifluoromethyl ketone (20 microM), had no significant effect on ADPR-stimulated TRPM2 activity. 3. Inhibition of TRPM2 whole-cell currents by ACA was voltage independent and accelerated at decreased pH. ACA was ineffective when applied intracellularly. The single-channel conductance was not changed during ACA treatment, suggesting a reduction of TRPM2 open probability by modulating channel gating. 4. ACA (20 microM) also blocked currents through human TRPM8 and TRPC6 expressed in HEK293 cells, while BPB (100 microM) was ineffective. TRPC6-mediated currents (IC50 = 2.3 microM) and TRPM8-induced Ca2+ signals (IC50 = 3.9 microM) were blocked in a concentration-dependent manner. 5. ADPR-induced currents in human U937 cells, endogeneously expressing TRPM2 protein, were fully suppressed by 20 microM ACA. 6. Our data indicate that ACA modulates the activity of different TRP channels independent of PLA2 inhibition. Owing to its high potency and efficacy ACA can serve, in combination with other blockers, as a useful tool for studying the unknown function of TRPM2 in native cells.

• The mammalian melastatin-related transient receptor potential cation channels: an overview.

  Authors: Robert Kraft, Christian Harteneck

  Pflügers Archiv : European journal of physiology. 11/2005; 451(1):204-11.

  The mammalian melastatin-related transient receptor potential (TRPM) subfamily contains eight members. TRPM proteins, consisting of six putative transmembrane domains and intracellular N and CThe mammalian melastatin-related transient receptor potential (TRPM) subfamily contains eight members. TRPM proteins, consisting of six putative transmembrane domains and intracellular N and C termini, form monovalent-permeable cation channels with variable selectivity for Ca(2+), Mg(2+) and other divalent cations. Some functions are linked to their individual cation selectivity: the highly divalent-permeable cation channels TRPM6 and TRPM7 are involved in the control of Mg(2+) influx, whereas the Ca(2+)-impermeable channels TRPM4 and TRPM5 modulate cellular Ca(2+) entry by determining the membrane potential. TRPM2, TRPM3 and TRPM8 mediate a direct influx of Ca(2+) in response to specific stimuli. Electrophysiological properties of the founding member, melastatin (TRPM1), are unexplored. The individual TRPM members are activated by different stimuli, including voltage, Ca(2+), temperature, cell swelling, lipid compounds and other endogenous or exogenous ligands. This review summarizes molecular features, activation mechanisms, biophysical properties and modulators of TRPM channels.

• Activation of the melastatin-related cation channel TRPM3 by D-erythro-sphingosine [corrected].

  Authors: Christian Grimm, Robert Kraft, Günter Schultz, Christian Harteneck

  Molecular pharmacology. 04/2005; 67(3):798-805.

  TRPM3, a member of the melastatin-like transient receptor potential channel subfamily (TRPM), is predominantly expressed in human kidney and brain. TRPM3 mediates spontaneous Ca2+ entry andTRPM3, a member of the melastatin-like transient receptor potential channel subfamily (TRPM), is predominantly expressed in human kidney and brain. TRPM3 mediates spontaneous Ca2+ entry and nonselective cation currents in transiently transfected human embryonic kidney 293 cells. Using measurements with the Ca2+-sensitive fluorescent dye fura-2 and the whole-cell patch-clamp technique, we found that D-erythro-sphingosine, a metabolite arising during the de novo synthesis of cellular sphingolipids, activated TRPM3. Other transient receptor potential (TRP) channels tested [classic or canonical TRP (TRPC3, TRPC4, TRPC5), vanilloid-like TRP (TRPV4, TRPV5, TRPV6), and melastatin-like TRP (TRPM2)] did not significantly respond to application of sphingosine. Sphingosine-induced TRPM3 activation was not mediated by inhibition of protein kinase C, depletion of intracellular Ca2+ stores, and intracellular conversion of sphingosine to sphingosine-1-phosphate. Although sphingosine-1-phosphate and ceramides had no effect, two structural analogs of sphingosine, dihydro-D-erythro-sphingosine and N,N-dimethyl-D-erythro-sphingosine, also activated TRPM3. Sphingolipids, including sphingosine, are known to have inhibitory effects on a variety of ion channels. Thus, TRPM3 is the first ion channel activated by sphingolipids.

• Expression of ether à go-go potassium channels in human gliomas.

  Authors: Stephan Patt, Katja Preussat, Christian Beetz, Robert Kraft, Michael Schrey, Rolf Kalff, Kristina Schönherr, Stefan H Heinemann

  Neuroscience letters. 10/2004; 368(3):249-53.

  Ether à go-go (EAG) K(+) channels have been shown to be involved in tumor generation and malignant growth. Gliomas have not been investigated thus far. Using RT-PCR we investigated healthy humanEther à go-go (EAG) K(+) channels have been shown to be involved in tumor generation and malignant growth. Gliomas have not been investigated thus far. Using RT-PCR we investigated healthy human brain and human gliomas of different subtypes and malignancy grades for the expression of human EAG1 and eag-related gene (ERG) 1 channels. mRNA of both channels was detected in all tissues. Expression was strong in normal brain, moderate in high-grade and high in low-grade gliomas. Our findings suggest a differential expression of hEAG1 and hERG1 in gliomas depending on the malignancy grade and nature of the tumor cells. However, the hypothesis that EAG channels are related to the oncogenic process itself is only partly supported by this study.

• Hydrogen peroxide and ADP-ribose induce TRPM2-mediated calcium influx and cation currents in microglia.

  Authors: Robert Kraft, Christian Grimm, Karin Grosse, Anja Hoffmann, Sophie Sauerbruch, Helmut Kettenmann, Günter Schultz, Christian Harteneck

  American journal of physiology. Cell physiology. 02/2004; 286(1):C129-37.

  Microglial cells are the host macrophages in the central nervous system and respond to brain injury and various neurological diseases. In this process, microglial cells undergo multiple morphologicalMicroglial cells are the host macrophages in the central nervous system and respond to brain injury and various neurological diseases. In this process, microglial cells undergo multiple morphological and functional changes from the resting cell toward a fully activated, phagocyting tissue macrophage. In culture, bacterial lipopolysaccharide (LPS) is a frequently used tool to induce this activation. By using calcium-imaging and patch-clamp techniques, we investigated the effect of hydrogen peroxide (H2O2), which is released by macrophagic cells themselves, on the intracellular calcium concentration and ion currents in cultured rat microglia. Application of 0.1-5 mM H2O2 for several minutes induced small responses in untreated cells but a large calcium influx and cation current in LPS-treated cells. In both untreated and LPS-treated microglia, internal perfusion of ADP-ribose (ADPR) via the patch pipette elicited large cation currents. Both stimuli, H2O2 and ADPR, have been reported to activate the recently cloned nonselective cation channel TRPM2. RT-PCR analysis from cultured rat glial and neuronal cells confirmed a strong expression of TRPM2 in rat microglia but not in astrocytes and cerebellar granule cells. In situ hybridizations from mouse brain showed a distribution of TRPM2, which is compatible with the expression in microglial cells. In conclusion, we describe here a novel calcium influx pathway in microglia coupled to hydrogen peroxide and ADPR and provide evidence that this pathway involves TRPM2. The increased sensitivity to H2O2 in LPS-stimulated cells suggests a role for TRPM2 in the calcium signaling of activated microglia.

• Expression of voltage-gated potassium channels Kv1.3 and Kv1.5 in human gliomas.

  Authors: Katja Preussat, Christian Beetz, Michael Schrey, Robert Kraft, Stefan Wölfl, Rolf Kalff, Stephan Patt

  Neuroscience letters. 08/2003; 346(1-2):33-6.

  K(+) channels play an important role in glial cell proliferation and are functionally expressed in glial tumors. Because voltage-gated K(+) channel (Kv) subtypes Kv1.3 and Kv1.5 have been shown toK(+) channels play an important role in glial cell proliferation and are functionally expressed in glial tumors. Because voltage-gated K(+) channel (Kv) subtypes Kv1.3 and Kv1.5 have been shown to contribute to growth-related properties of normal glia rather specifically, we investigated different human glioma samples for the expression of these channel subtypes using reverse transcriptase-PCR. Kv1.5 expression correlated with glioma entities and malignancy grades, i.e. expression was high in astrocytomas, moderate in oligodendrogliomas, and low in glioblastomas. No such correlation was evident for Kv1.3 expression. This study shows a clear differential expression of Kv1.5 in gliomas according to subtype and malignancy grade. This result corresponds to previous data on the expression of voltage-gated sodium channels in gliomas, which likewise showed a low or absent expression of channel subtypes in high-grade tumors.

• Molecular and functional characterization of the melastatin-related cation channel TRPM3.

  Authors: Christian Grimm, Robert Kraft, Sophie Sauerbruch, Günter Schultz, Christian Harteneck

  The Journal of biological chemistry. 07/2003; 278(24):21493-501.

  Proteins of the mammalian TRP (transient receptor potential) family form a heterogenous group of cation channels important for cellular Ca2+ signaling and homeostasis. Here we present the full-lengthProteins of the mammalian TRP (transient receptor potential) family form a heterogenous group of cation channels important for cellular Ca2+ signaling and homeostasis. Here we present the full-length sequence of TRPM3, a member of the melastatin-like subfamily (TRPM) of TRP channels. TRPM3 expression was found in human kidney and brain. HEK293 cells transiently transfected with TRPM3 showed a constitutive Ca2+ and Mn2+ entry. Whole-cell patch clamp experiments confirmed the spontaneous activity of TRPM3 and revealed permeability ratios PCa/PNa of 1.57 and PNa/PCs of 0.75. In cell-attached patches, spontaneous inward and outward currents were observed. At negative membrane potentials and in the presence of either 140 mm Cs+, 140 mm Na+, or 100 mm Ca2+ in the pipette solution, the single channel conductance levels were 133, 83, and 65 pS, respectively. The Ca2+ entry in TRPM3-expressing HEK293 cells increased during treatment with hypotonic extracellular solution. The reduction of extracellular osmolarity was accompanied by cell swelling, suggesting volume-regulated activity of TRPM3. From its function and expression in human kidney, we propose a role of TRPM3 in renal Ca2+ homeostasis.

• BK channel openers inhibit migration of human glioma cells.

  Authors: Robert Kraft, Peter Krause, Silke Jung, Daniel Basrai, Lutz Liebmann, Jürgen Bolz, Stephan Patt

  Pflügers Archiv : European journal of physiology. 06/2003; 446(2):248-55.

  Large-conductance Ca(2+)-activated K(+) channels (BK channels) are highly expressed in human glioma cells. However, less is known about their biological function in these cells. We used theLarge-conductance Ca(2+)-activated K(+) channels (BK channels) are highly expressed in human glioma cells. However, less is known about their biological function in these cells. We used the patch-clamp technique to investigate activation properties of BK channels and time-lapse microscopy to evaluate the role of BK channel activation in migration of 1321N1 human glioma cells. In whole cells, internal perfusion with a solution containing 500 nM free Ca(2+) and external application of the BK channel opener phloretin (100 micro M) shifted the activation threshold of BK channel currents toward more negative voltages of about -30 mV, which is close to the resting potential of the cells. The concentration of intracellular Ca(2+) in fura-2-loaded 1321N1 cells was measured to be 235+/-19 nM and was increased to 472+/-25 nM after treatment with phloretin. Phloretin and another BK channel opener NS1619 (100 micro M) reduced the migration velocity by about 50%. A similar reduction was observed following muscarinic stimulation of glioma cells with acetylcholine (100 micro M). The effects of phloretin, NS1619 and acetylcholine on cell migration were completely abolished by co-application of the specific BK channel blockers paxilline (5 micro M) and iberiotoxin (100 nM). The phloretin-induced increase in intracellular Ca(2+) was unaffected by the removal of extracellular Ca(2+) and co-application of paxilline. These findings indicate that glioma cell migration was inhibited through BK channel activation, independent of intracellular Ca(2+).

• Molecular characterization of voltage-gated sodium channels in human gliomas.

  Authors: Michael Schrey, Carolina Codina, Robert Kraft, Christian Beetz, Rolf Kalff, Stefan Wölfl, Stephan Patt

  Neuroreport. 01/2003; 13(18):2493-8.

  Voltage-sensitive sodium channels appear to be an electrophysiological hallmark of gliomas. However, the expression of channel subtypes is unclear in these tumors. In this study different gliomasVoltage-sensitive sodium channels appear to be an electrophysiological hallmark of gliomas. However, the expression of channel subtypes is unclear in these tumors. In this study different gliomas were investigated for the expression of sodium channel subtypes Na(v)1.1, Na(v)1.2, Na(v)1.3, Na(v)1.4, Na(v)1.6, and Na(x)(Na(v)2.1) using RT-PCR. At least one subtype of channels could be detected in each tumor. High-grade gliomas expressed fewer sodium channel subtypes and these at weaker levels than low-grade tumors. Expression of Na(v)1.6, the most abundant isoform in the CNS, was almost absent in the gliomas except the pilocytic variant. Our study gives clear evidence for a differential expression of sodium channel subtypes in gliomas and indicates a predominant expression of channels related to malignancy grades.

• BK channel blockers inhibit potassium-induced proliferation of human astrocytoma cells.

  Authors: Daniel Basrai, Robert Kraft, Christian Bollensdorff, Lutz Liebmann, Klaus Benndorf, Stephan Patt

  Neuroreport. 04/2002; 13(4):403-7.

  The functional role of BK channels, which are consistently expressed in glioma cells, is not clear. Here we show that the BK channels are regularly active in human 1321N1 astrocytoma cells atThe functional role of BK channels, which are consistently expressed in glioma cells, is not clear. Here we show that the BK channels are regularly active in human 1321N1 astrocytoma cells at physiological membrane potentials. The proliferation of the cells at the physiological external [K+] of 5 mM is compared with that at the elevated external [K+] of 20 mM, simulating the situation in rapidly growing, necrotic tumours in vivo. High extracellular [K+] in the range 10-30 mM significantly increases the proliferation of 1321N1 cells. This K+ induced proliferation can be completely abolished by applying the specific BK channel blockers iberiotoxin (IBTX) or 1 mM tetraethylammonium (TEA). Neither blocker has any effect on cell growth at 5 mM [K+]e. These findings indicate a particular role of BK channels in astrocytoma cell proliferation.

• Source Localization and Possible Causes of Interictal Epileptic Activity in Tumor-Associated Epilepsy

  Authors: Stephan Patt, Jörg Steenbeck, Albrecht Hochstetter, Robert Kraft, Ralf Huonker, Jens Haueisen, Nils Haberland, Kristian Ebmeier, Rudolf Hliscs, Jens Fiehler, Hannes Nowak, Rolf Kalff

  Neurobiology of Disease.

  Electrophysiological studies in gliomas have demonstrated action potentials in neoplastic cells. These “spiking tumor cells” are, however, an enigma. In attempt to find evidences for spikes withinElectrophysiological studies in gliomas have demonstrated action potentials in neoplastic cells. These “spiking tumor cells” are, however, an enigma. In attempt to find evidences for spikes within tumoral borders, 21 patients with different intracerebral tumors were preoperatively screened for the occurrence of epileptogenic discharges using multichannel MEG and EEG. A correlation between histopathology and the distance between dipole and tumor border could be found. Glioma patients showed epileptic activities closer to the border than those with mixed glioneuronal neoplasms and metastases. Four glioma patients demonstrated epileptic activity within the tumor boundary, however, not in the deep center of the tumor. Patch-clamping of cells from acute glioma slices did not yield a correlation between the presence of voltage-gated sodium channels in tumor cells and the MEG/EEG data. Our results demonstrate that the zone with the highest epileptogenic potential is different in gliomas and other brain tumors. However, our data do not strongly suggest that glioma cells are directly involved in the generation of tumor-associated epilepsy in vivo via their capability to generate action potentials.

• Voltage- and γ-aminobutyric acid-activated membrane currents in the human medulloblastoma cell line MHH-MED-3

  Authors: Carolina Codina, Robert Kraft, Torsten Pietsch, Marco Prinz, Christian Steinhäuser, Jorge Cervós-Navarro, Stephan Patt

  Neuroscience Letters.

  The whole-cell patch clamp technique was used to characterize voltage- and neurotransmitter-activated currents in the medulloblastoma cell line MHH-MED-3 and cells from tissue slices and primaryThe whole-cell patch clamp technique was used to characterize voltage- and neurotransmitter-activated currents in the medulloblastoma cell line MHH-MED-3 and cells from tissue slices and primary cultures of two medulloblastoma biopsies. These preparations revealed similar electrophysiological properties. All tested cells displayed 4-aminopyridine-sensitive delayed rectifying K+ currents, γ-aminobutyric acidA receptor-mediated Cl− currents and most of them inward rectifier K+ currents. Transient inward currents were mainly carried by low-voltage activated T-type Ca2+ channels in MHH-MED-3 cells, and tetrodotoxin-sensitive Na+ channels in cells from the primary culture. From these characteristics we conclude that medulloblastoma cells share physiological features with developing cerebellar granule cells at an immature stage.