Voltage-activated Potassium Currents Research Articles

Ambient noise exposure induces long-term adaptations in adult brainstem neurons

To counterbalance long-term environmental changes, neuronal circuits adapt the processing of sensory information. In the auditory system, ongoing background noise drives long-lasting adaptive mechanism in binaural coincidence detector neurons in the superior olive. However, the compensatory cellular mechanisms of the binaural neurons in the medial superior olive (MSO) to long-term background changes are unexplored. Here we investigated the cellular properties of MSO neurons during long-lasting adaptations induced by moderate omnidirectional noise exposure. After noise exposure, the input resistance of MSO neurons of mature Mongolian gerbils was reduced, likely due to an upregulation of hyperpolarisation-activated cation and low voltage-activated potassium currents. Functionally, the long-lasting adaptations increased the action potential current threshold and facilitated high frequency output generation. Noise exposure accelerated the occurrence of spontaneous postsynaptic currents. Together, our data suggest that cellular adaptations in coincidence detector neurons of the MSO to continuous noise exposure likely increase the sensitivity to differences in sound pressure levels.

In Vivo Attenuation of M-Current Suppression Impairs Consolidation of Object Recognition Memory.

The M-current is a low voltage-activated potassium current generated by neuronal Kv7 channels. A prominent role of the M-current is to a create transient increase of neuronal excitability in response to neurotransmitters through the suppression of this current. Accordingly, M-current suppression is assumed to be involved in higher brain functions including learning and memory. However, there is little evidence supporting such a role to date. To address this gap, we examined behavioral tasks to assess learning and memory in homozygous Kv7.2 knock-in mice, Kv7.2(S559A), which show reduced M-current suppression while maintaining a normal basal M-current activity in neurons. We found that Kv7.2(S559A) mice had normal object location memory and contextual fear memory, but impaired long-term object recognition memory. Furthermore, short-term memory for object recognition was intact in Kv7.2(S559A) mice. The deficit in long-term object recognition memory was restored by the administration of a selective Kv7 channel inhibitor, XE991, when delivered during the memory consolidation phase. Lastly, c-Fos induction 2 h after training in Kv7.2(S559A) mice was normal in the hippocampus, which corresponds to intact object location memory, but was reduced in the perirhinal cortex, which corresponds to impaired long-term object recognition memory. Together, these results support the overall conclusion that M-current suppression is important for memory consolidation of specific types of memories.SIGNIFICANCE STATEMENT Dynamic regulation of neuronal excitation is a fundamental mechanism for information processing in the brain, which is mediated by changes in synaptic transmissions or by changes in ion channel activity. Some neurotransmitters can facilitate action potential firing by suppression of a low voltage-activated potassium current, M-current. We demonstrate that M-current suppression is critical for establishment of long-term object recognition memory, but is not required for establishment of hippocampus-dependent location memory or contextual memory. This study suggests that M-current suppression is important for stable encoding of specific types of memories.

Inhibition of Kv2.1 Potassium Channels by MiDCA1, A Pre-Synaptically Active PLA2-Type Toxin from Micrurus dumerilii carinicauda Coral Snake Venom.

MiDCA1, a phospholipase A2 (PLA2) neurotoxin isolated from Micrurus dumerilii carinicauda coral snake venom, inhibited a major component of voltage-activated potassium (Kv) currents (41 ± 3% inhibition with 1 μM toxin) in mouse cultured dorsal root ganglion (DRG) neurons. In addition, the selective Kv2.1 channel blocker guangxitoxin (GxTx-1E) and MiDCA1 competitively inhibited the outward potassium current in DRG neurons. MiDCA1 (1 µM) reversibly inhibited the Kv2.1 current by 55 ± 8.9% in a Xenopus oocyte heterologous system. The toxin showed selectivity for Kv2.1 channels over all the other Kv channels tested in this study. We propose that Kv2.1 channel blockade by MiDCA1 underlies the toxin’s action on acetylcholine release at mammalian neuromuscular junctions.

Distinct Distribution Patterns of Potassium Channel Sub-Units in Somato-Dendritic Compartments of Neurons of the Medial Superior Olive.

Coincidence detector neurons of the medial superior olive (MSO) are sensitive to interaural time differences in the range of a few tens of microseconds. The biophysical basis for this remarkable acuity is a short integration time constant of the membrane, which is achieved by large low voltage-activated potassium and hyperpolarization-activated inward cation conductances. Additional temporal precision is thought to be achieved through a sub-cellular distribution of low voltage-activated potassium channel expression biased to the soma. To evaluate the contribution of potassium channels, we investigated the presence and sub-cellular distribution profile of seven potassium channel sub-units in adult MSO neurons of gerbils. We find that low- and high voltage-activated potassium channels are present with distinct sub-cellular distributions. Overall, low voltage-activated potassium channels appear to be biased to the soma while high voltage-activated potassium channels are more evenly distributed and show a clear expression at distal dendrites. Additionally, low voltage-activated potassium channel sub-units co-localize with glycinergic inputs while HCN1 channels co-localize more with high voltage-activated potassium channels. Functionally, high voltage-activated potassium currents are already active at low voltages near the resting potential. We describe a possible role of high voltage-activated potassium channels in modulating EPSPs in a computational model and contributing to setting the integration time window of coincidental inputs. Our data shows that MSO neurons express a large set of different potassium channels with distinct functional relevance.

SMITten for KCNQ Channels

Over the last two decades, members of the KCNQ channel family of potassium channels (KCNQ1–5) have emerged as critical regulators of cardiac and neuronal excitability (1,2). KCNQ1 channels are the molecular determinants of the cardiac slow potassium current, IKS (1), which is partly responsible for the repolarization of the cardiac action potential. Loss-of-function variants of KCNQ1 channels lead to a rare heart condition, long QT syndrome, and gain-of-function variants lead to atrial fibrillation.

Functional and neurochemical characterization of angiotensin type 1A receptor-expressing neurons in the nucleus of the solitary tract of the mouse.

Angiotensin II acts via two main receptors within the central nervous system, with the type 1A receptor (AT1AR) most widely expressed in adult neurons. Activation of the AT1R in the nucleus of the solitary tract (NTS), the principal nucleus receiving central synapses of viscerosensory afferents, modulates cardiovascular reflexes. Expression of the AT1R occurs in high density within the NTS of most mammals, including humans, but the fundamental electrophysiological and neurochemical characteristics of the AT1AR-expressing NTS neurons are not known. To address this, we have used a transgenic mouse, in which the AT1AR promoter drives expression of green fluorescent protein (GFP). Approximately one-third of AT1AR-expressing neurons express the catecholamine-synthetic enzyme tyrosine hydroxylase (TH), and a subpopulation of these stained for the transcription factor paired-like homeobox 2b (Phox2b). A third group, comprising approximately two-thirds of the AT1AR-expressing NTS neurons, showed Phox2b immunoreactivity alone. A fourth group in the ventral subnucleus expressed neither TH nor Phox2b. In whole cell recordings from slices in vitro, AT1AR-GFP neurons exhibited voltage-activated potassium currents, including the transient outward current and the M-type potassium current. In two different mouse strains, both AT1AR-GFP neurons and TH-GFP neurons showed similar AT1AR-mediated depolarizing responses to superfusion with angiotensin II. These data provide a comprehensive description of AT1AR-expressing neurons in the NTS and increase our understanding of the complex actions of this neuropeptide in the modulation of viscerosensory processing.

Alteration of Neuronal Excitability and Short-Term Synaptic Plasticity in the Prefrontal Cortex of a Mouse Model of Mental Illness.

Using a genetic mouse model that faithfully recapitulates a DISC1 genetic alteration strongly associated with schizophrenia and other psychiatric disorders, we examined the impact of this mutation within the prefrontal cortex. Although cortical layering, cytoarchitecture, and proteome were found to be largely unaffected, electrophysiological examination of the mPFC revealed both neuronal hyperexcitability and alterations in short-term synaptic plasticity consistent with enhanced neurotransmitter release. Increased excitability of layer II/III pyramidal neurons was accompanied by consistent reductions in voltage-activated potassium currents near the action potential threshold as well as by enhanced recruitment of inputs arising from superficial layers to layer V. We further observed reductions in both the paired-pulse ratios and the enhanced short-term depression of layer V synapses arising from superficial layers consistent with enhanced neurotransmitter release at these synapses. Recordings from layer II/III pyramidal neurons revealed action potential widening that could account for enhanced neurotransmitter release. Significantly, we found that reduced functional expression of the voltage-dependent potassium channel subunit Kv1.1 substantially contributes to both the excitability and short-term plasticity alterations that we observed. The underlying dysregulation of Kv1.1 expression was attributable to cAMP elevations in the PFC secondary to reduced phosphodiesterase 4 activity present in Disc1 deficiency and was rescued by pharmacological blockade of adenylate cyclase. Our results demonstrate a potentially devastating impact of Disc1 deficiency on neural circuit function, partly due to Kv1.1 dysregulation that leads to a dual dysfunction consisting of enhanced neuronal excitability and altered short-term synaptic plasticity.SIGNIFICANCE STATEMENT Schizophrenia is a profoundly disabling psychiatric illness with a devastating impact not only upon the afflicted but also upon their families and the broader society. Although the underlying causes of schizophrenia remain poorly understood, a growing body of studies has identified and strongly implicated various specific risk genes in schizophrenia pathogenesis. Here, using a genetic mouse model, we explored the impact of one of the most highly penetrant schizophrenia risk genes, DISC1, upon the medial prefrontal cortex, the region believed to be most prominently dysfunctional in schizophrenia. We found substantial derangements in both neuronal excitability and short-term synaptic plasticity-parameters that critically govern neural circuit information processing-suggesting that similar changes may critically, and more broadly, underlie the neural computational dysfunction prototypical of schizophrenia.

Transient voltage-activated K+ currents in central antennal lobe neurons: cell type-specific functional properties.

In this study we analyzed transient voltage-activated K+ currents (IA) of projection neurons and local interneurons in the antennal lobe of the cockroach Periplaneta americana The antennal lobe is the first synaptic processing station for olfactory information in insects. Local interneurons are crucial for computing olfactory information and form local synaptic connections exclusively in the antennal lobe, whereas a primary task of the projection neurons is the transfer of preprocessed olfactory information from the antennal lobe to higher order centers in the protocerebrum. The different physiological tasks of these neurons require specialized physiological and morphological neuronal phenotypes. We asked if and how the different physiological phenotypes are reflected in the functional properties of IA, which is crucial for shaping intrinsic electrophysiological properties of neurons. Whole cell patch-clamp recordings from adult male P. americana showed that all their central antennal lobe neurons can generate IA The current exhibited marked cell type-specific differences in voltage dependence of steady-state activation and inactivation, and differences in inactivation kinetics during sustained depolarization. Pharmacological experiments revealed that IA in all neuron types was partially blocked by α-dendrotoxin and phrixotoxin-2, which are considered blockers with specificity for Shaker- and Shal-type channels, respectively. These findings suggest that IA in each cell type is a mixed current generated by channels of both families. The functional role of IA was analyzed in experiments under current clamp, in which portions of IA were blocked by α-dendrotoxin or phrixotoxin-2. These experiments showed that IA contributes significantly to the intrinsic electrophysiological properties, such as the action potential waveform and membrane excitability.NEW & NOTEWORTHY In the insect olfactory system, projection neurons and local interneurons have task-specific electrophysiological and morphological phenotypes. Voltage-activated potassium channels play a crucial role in shaping functional properties of these neurons. This study revealed marked cell type-specific differences in the biophysical properties of transient voltage-activated potassium currents in central antennal lobe neurons.

Genistein inhibits hypoxia, ischemic-induced death, and apoptosis in PC12 cells.

A hypoxia/ischemia neuronal model was established in PC12 cells using oxygen-glucose deprivation (OGD). OGD-induced neuronal death, apoptosis, glutamate receptor subunit GluR2 expression, and potassium channel currents were evaluated in the present study to determine the effects of genistein in mediating the neuronal death and apoptosis induced by hypoxia and ischemia, as well as its underlying mechanism. OGD exposure reduced the cell viability, increased apoptosis, decreased the GluR2 expression, and decreased the voltage-activated potassium currents. Genistein partially reversed the effects induced by OGD. Therefore, genistein may prevent hypoxia/ischemic-induced neuronal apoptosis that is mediated by alterations in GluR2 expression and voltage-activated potassium currents.

Firing frequency and entrainment maintained in primary auditory neurons in the presence of combined BDNF and NT3.

Primary auditory neurons rely on neurotrophic factors for development and survival. We previously determined that exposure to brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT3) alters the activity of hyperpolarization-activated currents (Ih) in this neuronal population. Since potassium channels are sensitive to neurotrophins, and changes in Ih are often accompanied by a shift in voltage-gated potassium currents (IK), this study examined IK with exposure to both BDNF and NT3 and the impact on firing entrainment during high frequency pulse trains. Whole-cell patch-clamp recordings revealed significant changes in action potential latency and duration, but no change in firing adaptation or total outward IK. Dendrotoxin-I (DTX-I), targeting voltage-gated potassium channel subunits KV1.1 and KV1.2, uncovered an increase in the contribution of DTX-I sensitive currents with exposure to neurotrophins. No difference in Phrixotoxin-1 (PaTX-1) sensitive currents, mediated by KV4.2 and KV4.3 subunits, was observed. Further, no difference was seen in firing entrainment. These results show that combined BDNF and NT3 exposure influences the contribution of KV1.1 and KV1.2 to the low voltage-activated potassium current (IKL). Whilst this is accompanied by a shift in spike latency and duration, both firing frequency and entrainment to high frequency pulse trains are preserved.

Genistein inhibition of OGD-induced brain neuron death correlates with its modulation of apoptosis, voltage-gated potassium and sodium currents and glutamate signal pathway

In the present study, we established an in vitro model of hypoxic-ischemia via exposing primary neurons of newborn rats to oxygen–glucose deprivation (OGD) and observing the effects of genistein, a soybean isoflavone, on hypoxic-ischemic neuron viability, apoptosis, voltage-activated potassium (Kv) and sodium (Nav) currents, and glutamate receptor subunits. The results indicated that OGD exposure reduced the viability and increased the apoptosis of brain neurons. Meanwhile, OGD exposure caused changes in the current-voltage curves and current amplitude values of voltage-activated potassium and sodium currents; OGD exposure also decreased GluR2 expression and increased NR2 expression. However, genistein at least partially reversed the effects caused by OGD. The results suggest that hypoxic-ischemia-caused neuronal apoptosis/death is related to an increase in K+ efflux, a decrease in Na+ influx, a down-regulation of GluR2, and an up-regulation of NR2. Genistein may exert some neuroprotective effects via the modulation of Kv and Nav currents and the glutamate signal pathway, mediated by GluR2 and NR2.

Control of Phasic Firing by a Background Leak Current in Avian Forebrain Auditory Neurons.

Central neurons express a variety of neuronal types and ion channels that promote firing heterogeneity among their distinct neuronal populations. Action potential (AP) phasic firing, produced by low-threshold voltage-activated potassium currents (VAKCs), is commonly observed in mammalian brainstem neurons involved in the processing of temporal properties of the acoustic information. The avian caudomedial nidopallium (NCM) is an auditory area analogous to portions of the mammalian auditory cortex that is involved in the perceptual discrimination and memorization of birdsong and shows complex responses to auditory stimuli We performed in vitro whole-cell patch-clamp recordings in brain slices from adult zebra finches (Taeniopygia guttata) and observed that half of NCM neurons fire APs phasically in response to membrane depolarizations, while the rest fire transiently or tonically. Phasic neurons fired APs faster and with more temporal precision than tonic and transient neurons. These neurons had similar membrane resting potentials, but phasic neurons had lower membrane input resistance and time constant. Surprisingly phasic neurons did not express low-threshold VAKCs, which curtailed firing in phasic mammalian brainstem neurons, having similar VAKCs to other NCM neurons. The phasic firing was determined not by VAKCs, but by the potassium background leak conductances, which was more prominently expressed in phasic neurons, a result corroborated by pharmacological, dynamic-clamp, and modeling experiments. These results reveal a new role for leak currents in generating firing diversity in central neurons.

GDNF and NT-3 Induce Progenitor Bone Mesenchymal Stem Cell Differentiation into Neurons in Fetal Gut Culture Medium

With the increasing use of bone marrow mesenchymal stem cells (BMSCs) in cell therapies, factors regulating BMSC differentiation have become the interest of current research. In this study, we investigated the effects of glial cell-derived neurotrophic factor (GDNF) and neurotrophin-3 (NT-3) on the course of BMSC differentiation. BMSCs were isolated from rat bone marrow and transfected with GDNF and NT-3 genes. Compared to mock-transfected BMSCs, GDNF and NT-3 induced BMSC differentiation to reveal neuron-like characteristics, i.e., the positive expression of neuronal marker MAP-2 and astrocyte marker GFAP, as detected by immunofluorescence assays. Semi-quantitative polymerase chain reaction (PCR) and western blot analyses showed that the increase of expression of GDNF and NT-3 in BMSCs also simultaneously elevated the mRNA expression of NSE, nestin, and MAP-2. Furthermore, the cell patch-clamp test demonstrated that the overexpression of GDNF and NT-3 in BMSCs enhanced voltage-activated potassium currents, implying that BMSCs possess great potential as a cell-based therapeutic candidate to treat neurological diseases.

Multi-walled carbon nanotube increases the excitability of hippocampal CA1 neurons through inhibition of potassium channels in rat's brain slices

This study was to investigate the neurotoxicity of multi-walled carbon nanotube (MWCNT) by measuring neuronal excitability in rat hippocampal neurons and exploring the underlying mechanism. Whole cell patch-clamp technique was used. Action potential properties and the pattern of repetitive firing rate were assessed. Our data showed that spike half-width and repetitive firing rate were significantly increased in a concentration-dependent manner. Furthermore, voltage-activated potassium currents were recorded. It was found that MWCNT produced a concentration-dependent inhibition in amplitudes of IA and IK. In addition, MWCNT had effect on the activation kinetics of IA and IK with Vh being shifted to the negative potential at high concentration, while IA inactivation curve was considerably shifted to the hyperpolarize potential with Vh being increased. However, no effect was found on the recovery from inactivation of IA. The results suggest that MWCNT increases the excitability of hippocampal CA1 neurons by inhibiting voltage-gated potassium current.

Ca 2+ Entry Through TRP-C Channels Regulates Fibroblast Biology in Chronic Atrial Fibrillation

In this issue of Circulation , Harada et al1 provide fundamental new insights into the cellular mechanism(s) for initiation and maintenance of chronic atrial fibrillation in the human heart. The authors, taking what most might still consider to be an unconventional approach to understanding this proarrhythmic substrate,2,3,4 have identified the atrial fibroblast as an important player. More specifically, this international group of investigators concludes that a particular member of the transient receptor potential or TRP family5 of ion channels, TRPC3, when expressed/upregulated in human atrial fibroblasts, can contribute to chronic atrial fibrillation. Activation or enhanced expression of TRPC3 provides a means for increased transmembrane calcium entry into the fibroblast. This trigger calcium can then result in a marked increase in proliferation, followed by transformation to the myofibroblast phenotype.6,7 A previous study had drawn attention to the possibility that a different TRP channel subtype, TRPM7, could play a somewhat similar proarrhythmic role in the atrium.7,8 Article see p 2051 Atrial fibrillation is the most common form of cardiac arrhythmia in adult humans.9 Importantly, its incidence is projected to increase substantially as a consequence of the association of atrial fibrillation with healthy aging,10 diabetes mellitus, and hypothyroidism. Harada et al1 provide the first evidence for the presence of TRPC3 current during the proliferative phase in cultured human atrial fibroblasts. Knockdown of TRPC3 is able to suppress atrial fibroblast proliferation, and similar results were obtained with the pharmacological inhibitor PYR3, a relatively new pyrazole-based compound. This particular TRP channel exhibits significant calcium permeability. This calcium influx contributes to ERK phosphorylation, which is involved in mediating atrial fibroblast proliferation. A very interesting observation …

Comparison of the effects of DC031050, a class III antiarrhythmic agent, on hERG channel and three neuronal potassium channels

This study was conducted to test the selectivity of DC031050 on cardiac and neuronal potassium channels. Human ether-à-go-go related gene (hERG), KCNQ and Kv1.2 channels were expressed in CHO cells. The delayed rectifier potassium current (I(K)) was recorded from dissociated hippocampal pyramidal neurons of neonatal rats. Whole-cell voltage patch clamp was used to record the voltage-activated potassium currents. Drug-containing solution was delivered using a RSC-100 Rapid Solution Changer. Both DC031050 and dofetilide potently inhibited hERG currents with IC(50) values of 2.3 ± 1.0 and 17.9 ± 1.2 nmol/L, respectively. DC031050 inhibited the I(K) current with an IC(50) value of 2.7 ± 1.5 μmol/L, which was >1000 times the concentration required to inhibit hERG current. DC031050 at 3 μmol/L did not significantly affect the voltage-dependence of the steady activation, steady inactivation of I(K), or the rate of I(K) from inactivation. Intracellular application of DC031050 (5 μmol/L) was insufficient to inhibit I(K). DC031050 up to 10 μmol/L had no effects on KCNQ2 and Kv1.2 channel currents. DC031050 is a highly selective hERG potassium channel blocker with a substantial safety margin of activity over neuronal potassium channels, thus holds significant potential for therapeutic application as a class III antiarrhythmic agent.

The inhibitory effects of nano‐Ag on voltage‐gated potassium currents of hippocampal CA1 neurons

The application of the nano-sized materials continues to grow at a rapid rate in the fields of medicine, biotechnology, and environmental technology. Voltage-gated potassium currents play a key role in excitable cellular viability and function, especially in the central nervous system. The aim of this study was to investigate the actions of silver nano-particles (nano-Ag) on voltage-activated potassium currents in hippocampal CA1 neurons using whole cell patch-clamp technique. The hydrodynamic mean diameter of nano-Ag (10(-5) g mL(-1) ) was 223.9 nm in artificial cerebrospinal fluid (ACSF). Both types, transient potassium (I(A) ) and delayed rectifier potassium (I(K) ) current amplitudes were inhibited by the nano-Ag (10(-5) g mL(-1) ). The nano-Ag particles produced a hyperpolarizing shift in the activation-voltage curve of I(K) and inactivation-voltage curve of I(A) and also delayed the recovery of I(A) from inactivation. The results suggest that nano-Ag may have potential to alter the excitability of neurons by depressing the potassium channels.

Early Changes in Cerebellar Physiology Accompany Motor Dysfunction in the Polyglutamine Disease Spinocerebellar Ataxia Type 3

The relationship between cerebellar dysfunction, motor symptoms, and neuronal loss in the inherited ataxias, including the polyglutamine disease spinocerebellar ataxia type 3 (SCA3), remains poorly understood. We demonstrate that before neurodegeneration, Purkinje neurons in a mouse model of SCA3 exhibit increased intrinsic excitability resulting in depolarization block and the loss of the ability to sustain spontaneous repetitive firing. These alterations in intrinsic firing are associated with increased inactivation of voltage-activated potassium currents. Administration of an activator of calcium-activated potassium channels, SKA-31, partially corrects abnormal Purkinje cell firing and improves motor function in SCA3 mice. Finally, expression of the disease protein, ataxin-3, in transfected cells increases the inactivation of Kv3.1 channels and shifts the activation of Kv1.2 channels to more depolarized potentials. Our results suggest that in SCA3, early Purkinje neuron dysfunction is associated with altered physiology of voltage-activated potassium channels. We further suggest that the observed changes in Purkinje neuron physiology contribute to disease pathogenesis, underlie at least some motor symptoms, and represent a promising therapeutic target in SCA3.

Differentiation of Human Bone Marrow Mesenchymal Stem Cells into Neuron-Like Cells In Vitro

Responses of human mesenchymal stem cells from bone marrow (hBMSCs) were analyzed under chemical conditions, and then characterization of ion channels was evaluated by whole-cell patch clamp. To explore the possibility of differentiation of human bone marrow-derived mesenchymal stem cells into neuron-like cells in vitro under different conditions. The generation of mesenchymal stem cells into neuron-like cells has been studied. However, few of these studies characterized functional properties of the differentiated hBMSCs. hBMSCs (Passage 2) were expanded and cultured in vitro. After Passage 5 was subcultured, the cells were induced by cytokines and antioxidants. Morphologic observation, immunocytochemistry, Western blot analysis, and patch-clamp techniques were performed to evaluate properties of treated and control groups. The differentiated neuronal cells from hBMSCs not only expressed neuron phenotype and membrane channel protein including Nav1.6, Kv1.2, Kv1.3, and Cav1.2 but also exhibited functional ion currents. Both hBMSCs and differentiated cells expressed Nav1.6, Kv1.2, Kv1.3, and Cav1.2 and voltage-activated potassium currents, including delayed rectifier, noise-like and transient outward currents. However, expression of channel proteins, such as sodium channel Nav1.6 and potassium channels Kv1.2 and Kv1.3, were upregulated. Consistently, their potassium currents were also enhanced in the differentiated cells. hBMSCs possess of great potential to differentiate into functional neurons, indicating that hBMSCs may be an ideal cell source in managing a variety of clinical diseases such as spinal cord injury.

Into the role of insulin in neuronal activity

Event Abstract Back to Event Into the role of insulin in neuronal activity Pedro A. Lima1*, F. M. Alves1, A. Bastos1, A. M. Nascimento1, D. Ogden1 and P. F. Costa1 1 Faculdade Ciencias da Univerisidade de Lisboa, Centro de Quimica e Bioquimica, Portugal Insulin plays important functions in brain physiology and its receptors are distributed in specific brain areas such as olfactory bulb, hypothalamus and hippocampus. The role of brain insulin is unclear, although emerging data shows that insulin can enhance learning and memory. We postulate that such insulin mediated behavioural changes may result from insulin mediated alterations in neuroexcitability.We studied the effect of insulin on voltage activated potassium currents in acutely dissociated rat hippocampal CA1 pyramidal neurones and neuroblastoma cells, applying whole-cell voltage clamp techniques. Insulin inhibited slow voltage activated K+ currents (Islow) in both cell models. In CA1 neurons, the insulin sensitive current-component shows very slow inactivation (tau~1-3 s). Insulin (0.3nM) did not shift the steady state inactivation and activaction curves. Hence, insulin appears to be inhibiting Islow not via a change in channel kinetics. The channel identity of the insulin sensitive current has been determined with pharmacological tools. Most interestingly, insulin (300 nM) inhibits Islow (32.1% ±2.3; n=8) only in neurones in the post-prandrial phase (P21-P30 rats sacrificed 1 hour after eating, following overnight fasting); there was no detectable insulin evoked current reduction (up to 3 μM) in neurones from fasted rats (overnight) (n=12). The insulin effect is independent on experimental glucose availability. Preliminary data using antibodies against the InsRs suggest that the expression level is changing during the fed/fast cycle.Current–clamp recordings from CA1 pyramidal neurons conducted in fed rat brain slices showed that insulin (300 nM) determined an increase in spike frequency, and a decrease in threshold for action potential. Cell viability tests showed that insulin action in neuroexcitability is independent on the cellular processes related with insulin mediated neuroprotection. Additionally, photometric measurements and imaging from neurones loaded with Ca2+ sensitive dyes showed that insulin evoke transient increases in cytoplasmic Ca2+. This shows that insulin increases excitability in CA1 pyramidal hippocampal neurons by inhibiting a slow delayed rectifying K+ conductance, with implication to Ca2+ physiology. The relevance of such findings in the context of the insulin facilitatory effect on memory is under investigation and the significance of the insulin response dependency to the fed/fast cycle will be discussed. Conference: 11th Meeting of the Portuguese Society for Neuroscience, Braga, Portugal, 4 Jun - 6 Jun, 2009. Presentation Type: Poster Presentation Topic: Neuronal Communication Citation: Lima PA, Alves FM, Bastos A, Nascimento AM, Ogden D and Costa PF (2009). Into the role of insulin in neuronal activity. Front. Neurosci. Conference Abstract: 11th Meeting of the Portuguese Society for Neuroscience. doi: 10.3389/conf.neuro.01.2009.11.157 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 12 Aug 2009; Published Online: 12 Aug 2009. * Correspondence: Pedro A Lima, Faculdade Ciencias da Univerisidade de Lisboa, Centro de Quimica e Bioquimica, Lisboa, Portugal, plima.fisio@fcm.unl.pt Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Pedro A Lima F. M Alves A. Bastos A. M Nascimento D. Ogden P. F Costa Google Pedro A Lima F. M Alves A. Bastos A. M Nascimento D. Ogden P. F Costa Google Scholar Pedro A Lima F. M Alves A. Bastos A. M Nascimento D. Ogden P. F Costa PubMed Pedro A Lima F. M Alves A. Bastos A. M Nascimento D. Ogden P. F Costa Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.