Electrophysiology of mammalian inferior olivary neurones in vitro. Different types of voltage‐dependent ionic conductances.

Llinás, Rodolfó R.; Yarom, Yosef

doi:10.1113/jphysiol.1981.sp013763

Cited by 832 publications

(349 citation statements)

References 39 publications

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“…Significantly, our data are in close agreement with the reported electrophysiological parameters for the recombinant rat ␣ 1H gene (30). The presence of T-type Ca 2ϩ currents in PC12 cells was further confirmed by their rapid inactivation, another distinct feature of T-type Ca 2ϩ channels (27,32,35,36). Fig.…”

Section: Identification Of T-type Ca 2ϩ Channels In Pc12 Cells-pc12supporting

confidence: 90%

Induction of T-type Calcium Channel Gene Expression by Chronic Hypoxia

Toro

Levitsky

López‐Barneo

et al. 2003

Journal of Biological Chemistry

108

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Cellular responses to hypoxia can be acute or chronic. Acute responses mainly depend on oxygen-sensitive ion channels, whereas chronic responses rely on the hypoxia-inducible transcription factors (HIFs), which upregulate the expression of enzymes, transporters, and growth factors. It is unknown whether the expression of genes coding for ion channels is also influenced by hypoxia. We report here that the ␣ 1H gene of T-type voltage-gated calcium channels is highly induced by lowering oxygen tension in PC12 cells. Accumulation of ␣ 1H mRNA in response to hypoxia is time-and dose-dependent and paralleled by an increase in the density of Ttype calcium channel current recorded in patch clamped cells. HIF appears to be involved in the response to hypoxia, since cobalt chloride, desferrioxamine, and dimethyloxalylglycine, compounds that mimic HIF-regulated gene expression, replicate the hypoxic effect. Moreover, functional inhibition of HIF-2␣ protein accumulation using antisense HIF-2␣ oligonucleotides reverses the effect of hypoxia on T-type Ca 2؉ channel expression. Importantly, regulation by oxygen tension is specific for T-type calcium channels, since it is not observed with the L-, N-, and P/Q-channel types. These findings show for the first time that hypoxia induces an ion channel gene via a HIF-dependent mechanism and define a new role for the T-type calcium channels as regulators of cellular excitability and calcium influx under chronic hypoxia.Maintaining optimal oxygen homeostasis is of paramount importance for cells. Reductions of oxygen supply trigger cell adaptive responses that minimize the deleterious effects of hypoxia. Cellular responses to hypoxia can be acute, occurring over a time scale of seconds or minutes, or chronic, with time courses of hours to days (1-5). The major effectors of the acute cellular responses to hypoxia are oxygen-sensitive ion channels. These channels mediate the fast adaptive changes in cell excitability, contractility, and secretory activity that occur in response to low ambient oxygen tension (PO 2 ) (1, 5). On the other hand, chronic cellular responses to hypoxia, studied in great detail in the past few years, are mediated by ubiquitously expressed hypoxia-inducible transcription factors (HIF-1␣ 1 and isoforms). Stabilization and transcriptional activity of HIF depend on oxygen-regulated hydroxylases (6 -8). Hypoxia-inducible factors regulate the expression of a wide repertoire of oxygen-sensitive genes with roles in diverse cellular functions such as angiogenesis, red blood cell production, glucose and energy metabolism, apoptosis, and cell proliferation (1-5).Despite progress in the understanding of the role of ion channels and gene expression in the cellular responses to hypoxia, long term regulation of ion channel expression by maintained low PO 2 is poorly known. There are previous reports showing that prolonged hypoxia down-regulates various voltage-gated K ϩ (Kv) channel genes in pulmonary artery smooth muscle cells (9), and the opposite has been observed with the ...

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Section: Identification Of T-type Ca 2ϩ Channels In Pc12 Cells-pc12supporting

confidence: 90%

Induction of T-type Calcium Channel Gene Expression by Chronic Hypoxia

Toro

Levitsky

López‐Barneo

et al. 2003

Journal of Biological Chemistry

108

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“…In inferior olivary cells, this shoulder is mediated by high-threshold dendritic Ca 2+ currents. 35,36 Since pyramidal cells possess similar dendritic conductances, 30,67 and pyramidal neurons generate dendritic Ca 2+ plateaus in the presence of K + channel blockers, 53,67 a similar mechanism probably contributed to the spike shoulder observed here. In computer simulations of Cs + recordings, it was determined that Na + currents generated by the proximal 300 µm of the dendrites contributed to the falling phase of the somatic APs.…”

Section: Influence Of Inhibitory Postsynaptic Potentials On Somatofugmentioning

confidence: 73%

Inhibitory control of somatodendritic interactions underlying action potentials in neocortical pyramidal neurons in vivo: An intracellular and computational study

Paré¹,

Lang²,

Destexhe³

1998

Neuroscience

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Abstract--The effect of synaptic inputs on somatodendritic interactions during action potentials was investigated, in the cat, using in vivo intracellular recording and computational models of neocortical pyramidal cells. An array of 10 microelectrodes, each ending at a different cortical depth, was used to preferentially evoke synaptic inputs to different somatodendritic regions. Relative to action potentials evoked by current injection, spikes elicited by cortical microstimuli were reduced in amplitude and duration, with stimuli delivered at proximal (somatic) and distal (dendritic) levels evoking the largest and smallest decrements, respectively. When the inhibitory postsynaptic potential reversal was shifted to around 50 mV by recording with KCl pipettes, synaptically-evoked spikes were significantly less reduced than with potassium acetate or cesium acetate pipettes, suggesting that spike decrements are not only due to a shunt, but also to voltage-dependent effects. Computational models of neocortical pyramidal cells were built based on available data on the distribution of active currents and synaptic inputs in the soma and dendrites. The distribution of synapses activated by extracellular stimulation was estimated by matching the model to experimental recordings of postsynaptic potentials evoked at different depths. The model successfully reproduced the progressive spike amplitude reduction as a function of stimulation depth, as well as the effects of chloride and cesium. The model revealed that somatic spikes contain an important contribution from proximal dendritic sodium currents up to ]100 µm and ]300 µm from the soma under control and cesium conditions, respectively. Proximal inhibitory postsynaptic potentials can prevent this dendritic participation thus reducing the spike amplitude at the soma. The model suggests that the somatic spike amplitude and shape can be used as a ''window'' to infer the electrical participation of proximal dendrites.Thus, our results suggest that inhibitory postsynaptic potentials can control the participation of proximal dendrites in somatic sodium spikes.1998 IBRO. Published by Elsevier Science Ltd.Key words: multicompartment models, intrinsic electrophysiological properties, in vivo intracellular recordings, action potentials, dendritic integration.By comparing the shape of antidromic, orthodromic and current-evoked action potentials (APs) in motoneurons, Coombs et al. 7 provided compelling evidence for the idea that APs are initiated at the initial segment (IS) and then invade the somatodendritic compartment. However, the applicability of this model to other cell types was questioned when the first intradendritic recordings revealed that dendrites can sustain active electrogenesis. 33,34,63 In neocortical and hippocampal pyramidal neurons for instance, intracellular recordings revealed that dendritic spikes can be elicited by synaptic inputs 5,9,30,52 and that they can amplify synaptic inputs electrotonically distant from the soma to initiate APs. 5 Moreover, the prox...

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“…Inferior olivary (IO) neurons are electrotonically coupled via numerous gap junctions (Llinás and Yarom 1981;Llinás et al 1974;Sotelo et al 1974). Indeed, the density of neuronal gap junctions appears to be higher in the IO than in any other CNS region (Belluardo et al 2000;Condorelli et al 1998;De Zeeuw et al 1995).…”

Section: Introductionmentioning

confidence: 99%

Role of Myelination in the Development of a Uniform Olivocerebellar Conduction Time

Lang¹,

Rosenbluth

2003

Journal of Neurophysiology

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Lang, Eric J. and Jack Rosenbluth. Role of myelination in the development of a uniform olivocerebellar conduction time. J Neurophysiol 89: 2259 -2270, 2003. First published December 18, 2002 10.1152/jn.00922.2002. Purkinje cells generate simultaneous complex spikes as a result of olivocerebellar activity. This synchronization (to within 1 ms) is thought to result from electrotonic coupling of inferior olivary neurons. However, the distance from the inferior olive (IO) varies across the cerebellar cortex. Thus signals generated simultaneously at the IO should arrive asynchronously across the cerebellar cortex, unless the length differences are compensated for. Previously, it was shown that the conduction time from the IO to the cerebellar cortex remains nearly constant at Ϸ4 ms in the rat, implying the existence of such compensatory mechanisms. Here, we examined the role of myelination in generating a constant olivocerebellar conduction time by investigating the latency of complex spikes evoked by IO stimulation during development in normal rats and myelin-deficient mutants. In normal rats, myelination not only reduced overall olivocerebellar conduction time, but also disproportionately reduced the conduction time to vermal lobules, which had the longest response latencies prior to myelination. The net result was a nearly uniform conduction time. In contrast, in myelin-deficient rats, conduction time differences to different parts of the cerebellum remained during the same developmental period. Thus myelination is the primary factor in generating a uniform olivocerebellar conduction time. To test the importance of a uniform conduction time for generating synchronous complex spike activity, multiple electrode recordings were obtained from normal and myelin-deficient rats. Average synchrony levels were higher in normal rats than mutants. Thus the uniform conduction time achieved through myelination of olivocerebellar fibers appears to be essential for the normal expression of complex spike synchrony. I N T R O D U C T I O NInferior olivary (IO) neurons are electrotonically coupled via numerous gap junctions (Llinás and Yarom 1981;Llinás et al. 1974;Sotelo et al. 1974). Indeed, the density of neuronal gap junctions appears to be higher in the IO than in any other CNS region (Belluardo et al. 2000;Condorelli et al. 1998;De Zeeuw et al. 1995). This coupling allows IO neurons to generate precisely (on a millisecond time scale) synchronized activity that results in simultaneous complex spike (CS) activity in the cerebellum (Lang et al. 1999;Sasaki et al. 1989;Sugihara et al. 1993;Yamamoto et al. 2001).Maintenance of the synchronization present in IO discharges presents a challenge for the olivocerebellar system because the length of the olivocerebellar pathway to different points on the cerebellar cortex varies. In rats, there can be more than a twofold difference in the length of the olivocerebellar projection to different regions of the cortex (Sugihara et al. 1993). To preserve the precise synchronization present at...

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Electrophysiology of mammalian inferior olivary neurones in vitro. Different types of voltage‐dependent ionic conductances.

Cited by 832 publications

References 39 publications

Induction of T-type Calcium Channel Gene Expression by Chronic Hypoxia

Induction of T-type Calcium Channel Gene Expression by Chronic Hypoxia

Inhibitory control of somatodendritic interactions underlying action potentials in neocortical pyramidal neurons in vivo: An intracellular and computational study

Role of Myelination in the Development of a Uniform Olivocerebellar Conduction Time

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