Ionic basis of the resting membrane potential in cultured rat sympathetic neurons

Lamas, José Antonio; Reboreda, Antonio; Codesido, V.

doi:10.1097/00001756-200204160-00010

Cited by 32 publications

(31 citation statements)

References 25 publications

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“…While initially the muscarinic-sensitive potassium current (I M ) attracted most of the attention, soon other voltage-and non-voltage-dependant currents were shown to play an important role in the behaviour of sympathetic cells. The hyperpolarisationactivated cationic current (I h ), the voltage-insensitive resting current and the electrogenic component of the Na/K pump were all shown to contribute to the resting membrane potential in sympathetic cells [19][20]22]. Moreover, similar complexity was reported in hippocampal CA1 neurones [18].…”

Section: Introductionmentioning

confidence: 67%

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A riluzole- and valproate-sensitive persistent sodium current contributes to the resting membrane potential and increases the excitability of sympathetic neurones

Lamas

Romero

Reboreda

et al. 2009

Pflugers Arch - Eur J Physiol

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Non-adapting superior cervical ganglion (SCG) neurones with a clustering activity and sub-threshold membrane potential oscillations were occasionally recorded, suggesting the presence of a persistent sodium current (I(NaP)). The perforated-patch technique was used to establish its properties and physiological role. Voltage-clamp experiments demonstrated that all SCG cells have a TTX-sensitive I(NaP) activating at about -60 mV and with half-maximal activation at about -40 mV. The mean maximum I(NaP) amplitude was around -40 pA at -20 mV. Similar results were achieved when voltage steps or voltage ramps were used to construct the current-voltage relationships, and the general I(NaP) properties were comparable in mouse and rat SCG neurons. I(NaP) was inhibited by riluzole and valproate with an IC(50) of 2.7 and 3.8 microM, respectively, while both drugs inhibited the transient sodium current (I (NaT)) with a corresponding IC(50) of 34 and 150 microM. It is worth noting that 30 microM valproate inhibited the I(NaP) by 70% without affecting the I(NaT). In current clamp, valproate (30 microM) hyperpolarised resting SCG membranes by about 2 mV and increased the injected current necessary to evoke an action potential by about 20 pA. Together, these results demonstrate for the first time that a persistent sodium current exists in the membrane of SCG sympathetic neurones which could allow them to oscillate in the sub-threshold range. This current also contributes to the resting membrane potential and increases cellular excitability, so that it is likely to play an important role in neuronal behaviour.

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Section: Introductionmentioning

confidence: 67%

“…The resting membrane potential of SCG cells is finely tuned by the electrogenic activity of the Na/K pump and by several voltage-dependent and voltage-independent currents [22]. We propose that the persistent sodium current should be added to this complex model.…”

Section: Discussionmentioning

confidence: 99%

A riluzole- and valproate-sensitive persistent sodium current contributes to the resting membrane potential and increases the excitability of sympathetic neurones

Lamas

Romero

Reboreda

et al. 2009

Pflugers Arch - Eur J Physiol

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“…As a neuron differentiates and matures, the expression of ion channels, such as voltage-gated K + channels (K v ) and Na + channels (Na v ), shifts the RMP towards more negative potentials [39], [40], until it reaches about −65 mV in a mature neuron [41]. At this stage, the expression of specific Na v and K v in significant amounts drives the ability of neurons to generate APs.…”

Section: Resultsmentioning

confidence: 99%

A Time Course Analysis of the Electrophysiological Properties of Neurons Differentiated from Human Induced Pluripotent Stem Cells (iPSCs)

et al. 2014

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Many protocols have been designed to differentiate human embryonic stem cells (ESCs) and human induced pluripotent stem cells (iPSCs) into neurons. Despite the relevance of electrophysiological properties for proper neuronal function, little is known about the evolution over time of important neuronal electrophysiological parameters in iPSC-derived neurons. Yet, understanding the development of basic electrophysiological characteristics of iPSC-derived neurons is critical for evaluating their usefulness in basic and translational research. Therefore, we analyzed the basic electrophysiological parameters of forebrain neurons differentiated from human iPSCs, from day 31 to day 55 after the initiation of neuronal differentiation. We assayed the developmental progression of various properties, including resting membrane potential, action potential, sodium and potassium channel currents, somatic calcium transients and synaptic activity. During the maturation of iPSC-derived neurons, the resting membrane potential became more negative, the expression of voltage-gated sodium channels increased, the membrane became capable of generating action potentials following adequate depolarization and, at day 48–55, 50% of the cells were capable of firing action potentials in response to a prolonged depolarizing current step, of which 30% produced multiple action potentials. The percentage of cells exhibiting miniature excitatory post-synaptic currents increased over time with a significant increase in their frequency and amplitude. These changes were associated with an increase of Ca2+ transient frequency. Co-culturing iPSC-derived neurons with mouse glial cells enhanced the development of electrophysiological parameters as compared to pure iPSC-derived neuronal cultures. This study demonstrates the importance of properly evaluating the electrophysiological status of the newly generated neurons when using stem cell technology, as electrophysiological properties of iPSC-derived neurons mature over time.

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“…This finding is surprising as hyperpolarization is usually associated with a decrease in firing rate. Hyperpolarization may be a homeostatic response of infected neurons to significantly increased rates of depolarizing inputs [31],[32],[41]. This hypothesis suggests that when PRV induced AP and spikelet-like events begin, infected neurons compensate by shifting the balance of currents responsible for maintenance of membrane potential.…”

Section: Discussionmentioning

confidence: 99%

Pseudorabies Virus Infection Alters Neuronal Activity and Connectivity In Vitro

2009

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Alpha-herpesviruses, including human herpes simplex virus 1 & 2, varicella zoster virus and the swine pseudorabies virus (PRV), infect the peripheral nervous system of their hosts. Symptoms of infection often include itching, numbness, or pain indicative of altered neurological function. To determine if there is an in vitro electrophysiological correlate to these characteristic in vivo symptoms, we infected cultured rat sympathetic neurons with well-characterized strains of PRV known to produce virulent or attenuated symptoms in animals. Whole-cell patch clamp recordings were made at various times after infection. By 8 hours of infection with virulent PRV, action potential (AP) firing rates increased substantially and were accompanied by hyperpolarized resting membrane potentials and spikelet-like events. Coincident with the increase in AP firing rate, adjacent neurons exhibited coupled firing events, first with AP-spikelets and later with near identical resting membrane potentials and AP firing. Small fusion pores between adjacent cell bodies formed early after infection as demonstrated by transfer of the low molecular weight dye, Lucifer Yellow. Later, larger pores formed as demonstrated by transfer of high molecular weight Texas red-dextran conjugates between infected cells. Further evidence for viral-induced fusion pores was obtained by infecting neurons with a viral mutant defective for glycoprotein B, a component of the viral membrane fusion complex. These infected neurons were essentially identical to mock infected neurons: no increased AP firing, no spikelet-like events, and no electrical or dye transfer. Infection with PRV Bartha, an attenuated circuit-tracing strain delayed, but did not eliminate the increased neuronal activity and coupling events. We suggest that formation of fusion pores between infected neurons results in electrical coupling and elevated firing rates, and that these processes may contribute to the altered neural function seen in PRV-infected animals.

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Ionic basis of the resting membrane potential in cultured rat sympathetic neurons

Cited by 32 publications

References 25 publications

A riluzole- and valproate-sensitive persistent sodium current contributes to the resting membrane potential and increases the excitability of sympathetic neurones

A riluzole- and valproate-sensitive persistent sodium current contributes to the resting membrane potential and increases the excitability of sympathetic neurones

A Time Course Analysis of the Electrophysiological Properties of Neurons Differentiated from Human Induced Pluripotent Stem Cells (iPSCs)

Pseudorabies Virus Infection Alters Neuronal Activity and Connectivity In Vitro

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