Influence of external pH on two types of low-voltage-activated calcium currents in primary sensory neurons of rats

Pinchenko, V.; Kostyuk, P. G.; Kostyuk, E. P.

doi:10.1016/j.bbagen.2005.04.008

Cited by 8 publications

(5 citation statements)

References 12 publications

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“…These changes have a strong effect on the properties of many receptors and ion channels of the plasma membrane (see, for examples [13,14]). Although both low (LVA) and high (HVA) voltage-activated Ca 2+ channels are affected by pHo changes [2,22,25,30,37], little is known about the effects of pHo variations on the different HVA channels (namely the L, P/Q, N, and R types), since most of the studies have focused only on L-type Ca 2+ channels. HVA channels are complexes formed by the association of the pore-forming Cavα subunit with auxiliary subunits, of which the most important are Cavβ and Cavα2δ [7].…”

Section: Introductionmentioning

confidence: 99%

Two sets of amino acids of the domain I of Cav2.3 Ca2+ channels contribute to their high sensitivity to extracellular protons

Cens

Rousset

Charnet

2011

Pflugers Arch - Eur J Physiol

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Extracellular acidification decreases Ca(2+) current amplitude and produces a depolarizing shift in the activation potential (Va) of voltage-gated Ca(2+) channels (VGCC). These effects are common to all VGCC, but differences exist between Ca(2+) channel types and the underlying molecular mechanisms remain largely unknown. We report here that the changes in current amplitude induced by extracellular acidification or alkalinisation are more important for Cav2.3 R type than for Cav2.1 P/Q-type Ca(2+) channels. This difference results from a higher shift of Va combined with a modification of channel conductance. Although involved in the sensitivity of channel conductance to extracellular protons, neither the EEEE locus nor the divalent cation selectivity locus could explain the specificity of the pH effects. We show that this specificity involves two separate sets of amino acids within domain I of the Cavα subunit. Residues of the voltage sensor domain and residues in the pore domain mediate the effects of extracellular protons on Va and on channel conductance, respectively. These new insights are important for elucidating the molecular mechanisms that control VGCC gating and conductance and for understanding the role of extracellular protons in other channels or membrane-tethered enzymes with similar pore and/or voltage sensor domains.

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Section: Introductionmentioning

confidence: 99%

Two sets of amino acids of the domain I of Cav2.3 Ca2+ channels contribute to their high sensitivity to extracellular protons

Cens

Rousset

Charnet

2011

Pflugers Arch - Eur J Physiol

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“…Cells and Electrophysiology-HEK-293 cells stably transfected with human TRPM8 (HEK-293 M8 ) were cultured as described previously (19), and TRPM8 expression was induced with tetracycline 24 h before the start of the experiments (20 Neurons were isolated from the lumbar DRG of adult Wistar rats (250 -300 g) using an enzymatic digestion procedure described elsewhere (21). The cell suspension was plated onto Petri dishes filled with Dulbecco's modified Eagle's medium (Invitrogen) supplemented with 10% fetal calf serum and 8 g/ml gentamicine and incubated for up to 18 -24 h at 37°C in the 95% air 5% CO 2 atmosphere prior to using them in electrophysiological experiments.…”

Section: Methodsmentioning

confidence: 99%

The Transient Receptor Potential Channel TRPM8 Is Inhibited via the α2A Adrenoreceptor Signaling Pathway

Bavencoffe

Gkika

Kondratskyi

et al. 2010

Journal of Biological Chemistry

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The transient receptor potential channel melastatin member 8 (TRPM8) is expressed in sensory neurons, where it constitutes the main receptor of environmental innocuous cold (10 -25°C). Among several types of G protein-coupled receptors expressed in sensory neurons, G i -coupled ␣2A-adrenoreceptor (␣2A-AR), is known to be involved in thermoregulation; however, the underlying molecular mechanisms remain poorly understood. Here we demonstrated that stimulation of ␣2A-AR inhibited TRPM8 in sensory neurons from rat dorsal root ganglia (DRG). In addition, using specific pharmacological and molecular tools combined with patch-clamp current recordings, we found that in heterologously expressed HEK-293 (human embryonic kidney) cells, TRPM8 channel is inhibited by the G i protein/adenylate cyclase (AC)/cAMP/protein kinase A (PKA) signaling cascade. We further identified the TRPM8 S9 and T17 as two key PKA phosphorylation sites regulating TRPM8 channel activity. We therefore propose that inhibition of TRPM8 through the ␣2A-AR signaling cascade could constitute a new mechanism of modulation of thermosensation in both physiological and pathological conditions.

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“…In the first part of this study, we investigated the effects of acidosis alone on intracellular [Ca 2+ ] i in small capsaicin-sensitive neurones arising from dorsal root ganglia as these are thought to be responsible for sensing ischaemic conditions [ 17 , 68 , 88 ]. In the second part of the study, we have compounded the effects of acidosis with anoxia and aglycaemia since these conditions not only accompany ischaemia but can have profound effects upon Ca 2+ regulation in sensory neurones [ 34 , 55 , 69 , 75 ].…”

Section: Discussionmentioning

confidence: 99%

Acid-evoked Ca2+ signalling in rat sensory neurones: effects of anoxia and aglycaemia

Henrich

Buckler

2009

Pflugers Arch - Eur J Physiol

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Ischaemia excites sensory neurones (generating pain) and promotes calcitonin gene-related peptide release from nerve endings. Acidosis is thought to play a key role in mediating excitation via the activation of proton-sensitive cation channels. In this study, we investigated the effects of acidosis upon Ca2+ signalling in sensory neurones from rat dorsal root ganglia. Both hypercapnic (pHo 6.8) and metabolic–hypercapnic (pHo 6.2) acidosis caused a biphasic increase in cytosolic calcium concentration ([Ca2+]i). This comprised a brief Ca2+ transient (half-time approximately 30 s) caused by Ca2+ influx followed by a sustained rise in [Ca2+]i due to Ca2+ release from caffeine and cyclopiazonic acid-sensitive internal stores. Acid-evoked Ca2+ influx was unaffected by voltage-gated Ca2+-channel inhibition with nickel and acid sensing ion channel (ASIC) inhibition with amiloride but was blocked by inhibition of transient receptor potential vanilloid receptors (TRPV1) with (E)-3-(4-t-butylphenyl)-N-(2,3-dihydrobenzo[b][1,4] dioxin-6-yl)acrylamide (AMG 9810; 1 μM) and N-(4-tertiarybutylphenyl)-4-(3-cholorphyridin-2-yl) tetrahydropryazine-1(2H)-carbox-amide (BCTC; 1 μM). Combining acidosis with anoxia and aglycaemia increased the amplitude of both phases of Ca2+ elevation and prolonged the Ca2+ transient. The Ca2+ transient evoked by combined acidosis, aglycaemia and anoxia was also substantially blocked by AMG 9810 and BCTC and, to a lesser extent, by amiloride. In summary, the principle mechanisms mediating increase in [Ca2+]i in response to acidosis are a brief Ca2+ influx through TRPV1 followed by sustained Ca2+ release from internal stores. These effects are potentiated by anoxia and aglycaemia, conditions also prevalent in ischaemia. The effects of anoxia and aglycaemia are suggested to be largely due to the inhibition of Ca2+-clearance mechanisms and possible increase in the role of ASICs.Electronic supplementary materialThe online version of this article (doi:10.1007/s00424-009-0715-6) contains supplementary material, which is available to authorized users.

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Influence of external pH on two types of low-voltage-activated calcium currents in primary sensory neurons of rats

Cited by 8 publications

References 12 publications

Two sets of amino acids of the domain I of Cav2.3 Ca2+ channels contribute to their high sensitivity to extracellular protons

Two sets of amino acids of the domain I of Cav2.3 Ca2+ channels contribute to their high sensitivity to extracellular protons

The Transient Receptor Potential Channel TRPM8 Is Inhibited via the α2A Adrenoreceptor Signaling Pathway

Acid-evoked Ca2+ signalling in rat sensory neurones: effects of anoxia and aglycaemia

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