Low threshold T‐type calcium current in rat embryonic chromaffin cells

Bournaud, Roland; Hidalgo, Jorge; Yu, Hua; Jaimovich, Enrique; Shimahara, Takeshi

doi:10.1111/j.1469-7793.2001.0035k.x

Cited by 39 publications

(43 citation statements)

References 37 publications

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“…Likewise, T-type Ca 2ϩ channels have not been detected in chromaffin cells until recently by using molecular approaches and analysis on different stages of cellular development. Remarkably, the T-type channels expressed in rat chromaffin cells share properties with the ␣ 1H subunit (55). These data are in good agreement with studies showing that the ␣ 1H subunit is mostly expressed in peripheral tissues (53), in contrast with ␣ 1G and ␣ 1I subunits that are more abundant in the brain (52,56).…”

Section: Discussionsupporting

confidence: 80%

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: Discussionsupporting

confidence: 80%

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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“…T-type channels are reported to coexist in bovine chromaYn cells (GarciaPalomero et al 2000), in a restricted proportion of adult rat chromaYn cells (Hollins and Ikeda 1996) and in a subpopulation of developing immature rat chromaYn cells (Bournaud et al 2001). In this latter case, T-type channels fail to support secretion, not because of insuYcient Ca 2+ inXux, but presumably because Ca 2+ entering could be rapidly buVered, limiting the raise of intracellular Ca 2+ to threshold levels required for triggering exocytosis.…”

Section: Discussionmentioning

confidence: 99%

Fast exocytosis mediated by T- and L-type channels in chromaffin cells: distinct voltage-dependence but similar Ca2+-dependence

et al. 2007

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Expression, spatial distribution and speciWc roles of diVerent Ca 2+ channels in stimulus-secretion coupling of chromaYn cells are intriguing issues still open to discussion. Most of the evidence supports a role of high-voltage activated (HVA) Ca 2+ channels (L-, N-, P/Q-and R-types) in the control of exocytosis: some suggesting a preferential coupling of speciWc Ca 2+ channel subunits with the secretory apparatus, others favoring the idea of a contribution to secretion proportional to the expression density and gating properties of Ca 2+ channels. In this work we review recent Wndings and bring new evidence in favor of the hypothesis that also the LVA (low-voltage-activated, T-type) Ca 2+ channels eVectively control fast exocytosis near resting potential in adrenal chromaYn cells of adult rats. Ttype channels recruited after long-term treatments with pCPT-cAMP (or chronic hypoxia) are shown to control exocytosis with the same eYcacy of L-type channels, which are the dominant Ca 2+ channel types expressed in rodent chromaYn cells. A rigorous comparison of T-and L-type channel properties shows that, although operating at diVerent potentials and with diVerent voltage-sensitivity, the two channels possess otherwise similar Ca 2+ -dependence of exocytosis, size and kinetics of depletion of the immediately releasable pool and mobilize vesicles of the same quantal size. Thus, T-and L-type channels are coupled with the same Ca 2+ -eYciency to the secretory apparatus and deplete the same number of vesicles ready for release.The major diVerence of the secretory signals controlled by the two channels appear to be the voltage range of operation, suggesting the idea that stressful conditions (hypoxia and persistent -adrenergic stimulation) can lower the threshold of cell excitability by recruiting new Ca 2+ channels and activate an additional source of catecholamine secretion.

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“…In embryonic RCCs, LVA channels are expressed in half of the cells but Ca 2+ currents through these channels elicited by 160 ms pulse depolarizations are not able to evoke sizable secretion [7]. On the contrary, secretion measured by capacitance changes and amperometric detection is evident in the other half of cells expressing HVA channels, thus suggesting that vesicles and the overall secretory apparatus is effectively coupled to voltage-gated Ca 2+ channels.…”

Section: T-type Channels and Fast Capacitance Changes In Rat Melanotrmentioning

confidence: 94%

T-type channels-secretion coupling: evidence for a fast low-threshold exocytosis

Carbone¹,

Marcantoni²,

Giancippoli³

et al. 2006

Pflugers Arch - Eur J Physiol

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T-type channels are transient low-voltage-activated (LVA) Ca 2+ channels that control Ca 2+ entry in excitable cells during small depolarizations around resting potential. Studies in the past 20 years focused on the biophysical, physiological, and molecular characterization of T-type channels in most tissues. This led to a welldefined picture of the functional role of LVA channels in controlling low-threshold spikes, oscillatory cell activity, muscle contraction, hormone release, cell growth and differentiation. So far, little attention has been devoted to the role of T-type channels in transmitter release, which mainly involves channel types belonging to the highvoltage-activated (HVA) Ca 2+ channel family. However, evidence is accumulating in favor of a unique participation of T-type channels in fast transmitter release. Clear data are now reported in reciprocal synapses of the retina and olfactory bulb, synaptic contacts between primary afferent and second order nociceptive neurons, rhythmic inhibitory interneurons of invertebrates and clonal cell lines transfected with recombinant α 1 channel subunits. T-type channels also regulate the large dense-core vesicle release of neuroendocrine cells where Ca 2+ dependence, rate of vesicle release, and size of readily releasable pool appear comparable to those associated to HVA channels. This suggests that when sufficiently expressed and properly located near the release zones, T-type channels can trigger fast low-threshold secretion. In this study, we will review the main findings that assign a specific task to T-type channels in fast exocytosis, discussing their possible involvement in the control of the Ca 2+ -dependent processes regulating exocytosis like vesicle depletion and vesicle recycling.

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Low threshold T‐type calcium current in rat embryonic chromaffin cells

Cited by 39 publications

References 37 publications

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

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

Fast exocytosis mediated by T- and L-type channels in chromaffin cells: distinct voltage-dependence but similar Ca2+-dependence

T-type channels-secretion coupling: evidence for a fast low-threshold exocytosis

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