l-Glutamate suppresses HVA calcium current in catfish horizontal cells by raising intracellular proton concentration

Dixon, Donald B.; Takahashi, Kyoh-Ichi; Copenhagen, David R.

doi:10.1016/0896-6273(93)90183-r

Cited by 59 publications

(41 citation statements)

References 43 publications

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“…Besides effects on cellular survival (45) or modulation of virtually all enzymatic activities, more specific effects may be exerted in the TRPV1-expressing free nerve endings, including a modulation of the conversion of the generator potential to action potentials or their further propagation along the axon. In line with this assumption, lowering the intracellular pH has been demonstrated to suppress the activity of high threshold voltage-gated Ca 2ϩ channels in sensory DRG neurons (46,47) as well as in other neuronal systems (48,49). Moreover, we could demonstrate that intracellular acidification modulates TRPV1 activity by inducing a voltage-dependent block taking effect mainly at potentials higher than Ϫ30 mV.…”

Section: Capsaicin-induced Changes Of the Ph I In Rat Dorsal Rootsupporting

confidence: 66%

TRPV1 Acts as Proton Channel to Induce Acidification in Nociceptive Neurons

Hellwig

Plant

Janson

et al. 2004

Journal of Biological Chemistry

141

101

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The low extracellular pH of inflamed or ischemic tissues enhances painful sensations by sensitizing and activating the vanilloid receptor 1 (TRPV1). We report here that activation of TRPV1 results in a marked intracellular acidification in nociceptive dorsal root ganglion neurons and in a heterologous expression system. A characterization of the underlying mechanisms revealed a Ca 2؉ -dependent intracellular acidification operating at neutral pH and an additional as yet unrecognized direct proton conductance through the poorly selective TRPV1 pore operating in acidic extracellular media. Large organic cations permeate through the activated TRPV1 pore even in the presence of physiological concentrations of Na ؉ , Mg 2؉ , and Ca 2؉ . The wide pore and the unexpectedly high proton permeability of TRPV1 point to a proton hopping permeation mechanism along the water-filled channel pore. In acidic media, the high relative proton permeability through TRPV1 defines a novel proton entry mechanism in nociceptive neurons.During ischemia or inflammation, pain sensation is augmented by the acidic extracellular pH (pH ext ). 1 A␦-and C-fiber neurons sense extracellular acid by means of two different classes of cation channels, namely TRPV1, the founding member of the vanilloid receptor-like transient receptor potential channel family (1, 2), and the acid-sensing ion channels (ASIC) (3, 4). Both channel types are expressed in small diameter dorsal root ganglion (DRG) neurons, and their role in mediating inflammatory hyperalgesia has been proven by gene deletion techniques (5-7). TRPV1, a poorly selective cation channel, integrates multiple pain-inducing stimuli, including noxious heat, vanilloids, and acidic extracellular pH (1, 8 -10). Inflammatory mediators such as bradykinin, serotonin, histamine, or prostaglandins further stimulate TRPV1 activity either by protein kinase C-dependent signals (11-13), by a release from a phosphatidylinositol 4,5-bisphosphate-dependent inhibition (14,15), by formation of 12-lipoxygenase products (16), or by a protein kinase A-mediated recovery from inactivation (17). Furthermore, extracellular acidification shifts the activation of TRPV1 toward lower temperature or ligand thresholds by protonation of an amino acid located in the vicinity of the pore loop (18). Although the role of the external pH ext in modulating TRPV1 activity is well established, a possible impact of TRPV1 activation on the intracellular pH has not been studied.A Ca 2ϩ influx component through activated voltage-or ligand-gated cation channels has been recognized to lower the intracellular pH (pH i ) in neurons or in neuroendocrine cells (19,20). We therefore asked the question whether activation of the Ca 2ϩ -permeable TRPV1 may also mediate intracellular acidification in native rat dorsal root ganglion neurons or in a heterologous expression system. Our results provide evidence for two independent TRPV1-mediated acidification signals, including an as yet unrecognized direct proton conductance through the activated TRPV1 p...

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Section: Capsaicin-induced Changes Of the Ph I In Rat Dorsal Rootsupporting

confidence: 66%

TRPV1 Acts as Proton Channel to Induce Acidification in Nociceptive Neurons

Hellwig

Plant

Janson

et al. 2004

Journal of Biological Chemistry

141

101

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“…These measurements are consistent with the general principal that depolarization increases metabolic load on cells, and this leads to an increase in the production and extrusion of protons. Two reports suggest that glutamate reduces proton efflux from isolated HCs (Dixon et al, 1993;Molina et al, 2004), a finding in contrast to what this proton model of feedback requires. This efflux is coupled to CaATPase activity and is observed when cells are bathed in a strongly pH-buffered environment (a proton sink).…”

Section: Horizontal Cells Could Modulate Cleft Ph Via An Amiloridesenmentioning

confidence: 41%

“…At the holding potential of Ϫ60 mV, the reduction in current from 94 to 60 pA was significant. Glutamate has complex effects on HCs, modulating inward rectification (Kaneko and Tachibana, 1985), increasing AMPA and kainate receptor activity (Lasater, 1986;Shingai and Christensen, 1986), suppressing Ca channel activity via intracellular acidification (Dixon et al, 1993), and enhancing outward rectification (Tachibana, 1983). We are not yet certain of the identity of the amiloride-sensitive conductance, and it will require investigation beyond the scope of this present work to be determined.…”

Section: Isolated Hcs Contain An Amiloride-sensitive Conductancementioning

confidence: 99%

Proton-Mediated Feedback Inhibition of Presynaptic Calcium Channels at the Cone Photoreceptor Synapse

Vessey

Stratis²,

Daniels³

et al. 2005

J. Neurosci.

117

136

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Generation of center-surround antagonistic receptive fields in the outer retina occurs via inhibitory feedback modulation of presynaptic voltage-gated calcium channels in cone photoreceptor synaptic terminals. Both conventional and unconventional neurotransmitters, as well as an ephaptic effect, have been proposed, but the intercellular messaging that mediates the inhibitory feedback signal from postsynaptic horizontal cells (HCs) to cones remains unknown. We examined the possibility that proton concentration in the synaptic cleft is regulated by HCs and that it carries the feedback signal to cones. In isolated, dark-adapted goldfish retina, we assessed feedback in the responses of HCs to light and found that strengthened pH buffering reduced both rollback and the depolarization to red light. In zebrafish retinal slices loaded with Fluo-4, depolarization with elevated K ϩ increased Ca signals in the synaptic terminals of cone photoreceptors. Kainic acid, which depolarizes HCs but has no direct effect on cones, depressed the K ϩ -induced Ca signal, whereas CNQX, which hyperpolarizes HCs, increased the Ca signals, suggesting that polarization of HCs alters inhibitory feedback to cones. We found that these feedback signals were blocked by elevated extracellular pH buffering, as well as amiloride and divalent cations. Voltage clamp of isolated HCs revealed an amiloride-sensitive conductance that could mediate modulation of cleft pH dependent on the membrane potential of these postsynaptic cells.

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“…On the other hand, under normal conditions the pH i is decreased after prolonged neuronal activity (Chesler and Kaila, 1992). In addition, NMDA is reported to reduce neuronal pH i in central neurons and in spinal motoneurons (Edres et al, 1986;Dixon et al, 1993;Hartley and Dubinsky, 1993;Irwin et al, 1994). Whether the NMDA receptor is modulated by intracellular pH shifts is still unknown.…”

Section: Abstract: Nmda Receptor; Nmda-induced Current; Intracellulamentioning

confidence: 99%

Regulation of Presynaptic NMDA Responses by External and Intracellular pH Changes at Developing Neuromuscular Synapses

Chen¹,

Fu³

1998

J. Neurosci.

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NMDA receptors play important roles in synaptic plasticity and neuronal development. The functions of NMDA receptors are modulated by many endogenous substances, such as external pH (pH e ), as well as second messenger systems. In the present study, the nerve-muscle cocultures of Xenopus embryos were used to investigate the effects of both external and intracellular pH (pH i ) changes on the functional responses of presynaptic NMDA receptors. Spontaneous synaptic currents (SSCs) were recorded from innervated myocyte using whole-cell recordings. Local perfusion of NMDA at synaptic regions increased the SSC frequency via the activation of presynaptic NMDA receptors. A decrease in pH e from 7.6 to 6.6 reduced NMDA responses to 23% of the control, and an increase in pH e from 7.6 to 8.6 potentiated the NMDA responses in increasing SSC frequency.

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l-Glutamate suppresses HVA calcium current in catfish horizontal cells by raising intracellular proton concentration

Cited by 59 publications

References 43 publications

TRPV1 Acts as Proton Channel to Induce Acidification in Nociceptive Neurons

TRPV1 Acts as Proton Channel to Induce Acidification in Nociceptive Neurons

Proton-Mediated Feedback Inhibition of Presynaptic Calcium Channels at the Cone Photoreceptor Synapse

Regulation of Presynaptic NMDA Responses by External and Intracellular pH Changes at Developing Neuromuscular Synapses

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