Pre- and post-synaptic effects of manipulating surface charge with divalent cations at the photoreceptor synapse

L. Cadetti, Wallace B Thoreson, M. Piccolino

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Persistence of horizontal cell (HC) light responses in extracellular solutions containing low Ca 2+ plus divalent cations to block Ca 2+ currents (I Ca) has been attributed to Ca 2+-independent neurotransmission. Using a retinal slice preparation to record both I Ca and light responses, we demonstrate that persistence of HC responses in low [Ca 2+] o can instead be explained by a paradoxical increase of Ca 2+ influx into photoreceptor terminals arising from surface charge-mediated shifts in I Ca activation. Consistent with this explanation, application of Zn 2+ or Ni 2+ caused a hyperpolarizing block of HC light responses that was relieved by lowering [Ca 2+] o. The same concentrations of Zn 2+ and Ni 2+ reduced the amplitude of I Ca at the rod dark potential and this reduction was relieved by a hyperpolarizing shift in voltage dependence induced by lowering [Ca 2+] o. Block of I Ca by Mg 2+, which has weak surface charge effects, was not relieved by low [Ca 2+] o. Recovery of HC responses in low [Ca 2+] o was assisted by enhancement of rod light responses. To bypass light stimulation, OFF bipolar cells were stimulated by steps to -40 mV applied to presynaptic rods during simultaneous paired recordings. Consistent with surface charge theory, the post-synaptic current was inhibited by Zn 2+ and this inhibition was relieved by lowering [Ca 2+] o. Nominally divalent-free media produced inversion of HC light responses even though rod light responses remained hyperpolarizing; HC response inversion can be explained by surface charge-mediated shifts in I Ca. In summary, HC light responses modifications induced by low divalent cation solutions can be explained by effects on photoreceptor light responses and membrane surface charge without necessitating Ca 2+-independent neurotransmission. Furthermore, these results suggest that surface charge effects accompanying physiological changing divalent cation levels in the synaptic cleft may provide a means for modulating synaptic output from photoreceptors.

Original languageEnglish (US)
Pages (from-to)791-801
Number of pages11
JournalNeuroscience
Volume129
Issue number3
DOIs
StatePublished - Nov 23 2004

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Divalent Cations
Synapses
Light
Synaptic Transmission
Membranes

Keywords

  • Mg
  • Ni
  • Zn
  • horizontal cell
  • retina

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Pre- and post-synaptic effects of manipulating surface charge with divalent cations at the photoreceptor synapse. / Cadetti, L.; Thoreson, Wallace B; Piccolino, M.

In: Neuroscience, Vol. 129, No. 3, 23.11.2004, p. 791-801.

Research output: Contribution to journalArticle

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abstract = "Persistence of horizontal cell (HC) light responses in extracellular solutions containing low Ca 2+ plus divalent cations to block Ca 2+ currents (I Ca) has been attributed to Ca 2+-independent neurotransmission. Using a retinal slice preparation to record both I Ca and light responses, we demonstrate that persistence of HC responses in low [Ca 2+] o can instead be explained by a paradoxical increase of Ca 2+ influx into photoreceptor terminals arising from surface charge-mediated shifts in I Ca activation. Consistent with this explanation, application of Zn 2+ or Ni 2+ caused a hyperpolarizing block of HC light responses that was relieved by lowering [Ca 2+] o. The same concentrations of Zn 2+ and Ni 2+ reduced the amplitude of I Ca at the rod dark potential and this reduction was relieved by a hyperpolarizing shift in voltage dependence induced by lowering [Ca 2+] o. Block of I Ca by Mg 2+, which has weak surface charge effects, was not relieved by low [Ca 2+] o. Recovery of HC responses in low [Ca 2+] o was assisted by enhancement of rod light responses. To bypass light stimulation, OFF bipolar cells were stimulated by steps to -40 mV applied to presynaptic rods during simultaneous paired recordings. Consistent with surface charge theory, the post-synaptic current was inhibited by Zn 2+ and this inhibition was relieved by lowering [Ca 2+] o. Nominally divalent-free media produced inversion of HC light responses even though rod light responses remained hyperpolarizing; HC response inversion can be explained by surface charge-mediated shifts in I Ca. In summary, HC light responses modifications induced by low divalent cation solutions can be explained by effects on photoreceptor light responses and membrane surface charge without necessitating Ca 2+-independent neurotransmission. Furthermore, these results suggest that surface charge effects accompanying physiological changing divalent cation levels in the synaptic cleft may provide a means for modulating synaptic output from photoreceptors.",
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N2 - Persistence of horizontal cell (HC) light responses in extracellular solutions containing low Ca 2+ plus divalent cations to block Ca 2+ currents (I Ca) has been attributed to Ca 2+-independent neurotransmission. Using a retinal slice preparation to record both I Ca and light responses, we demonstrate that persistence of HC responses in low [Ca 2+] o can instead be explained by a paradoxical increase of Ca 2+ influx into photoreceptor terminals arising from surface charge-mediated shifts in I Ca activation. Consistent with this explanation, application of Zn 2+ or Ni 2+ caused a hyperpolarizing block of HC light responses that was relieved by lowering [Ca 2+] o. The same concentrations of Zn 2+ and Ni 2+ reduced the amplitude of I Ca at the rod dark potential and this reduction was relieved by a hyperpolarizing shift in voltage dependence induced by lowering [Ca 2+] o. Block of I Ca by Mg 2+, which has weak surface charge effects, was not relieved by low [Ca 2+] o. Recovery of HC responses in low [Ca 2+] o was assisted by enhancement of rod light responses. To bypass light stimulation, OFF bipolar cells were stimulated by steps to -40 mV applied to presynaptic rods during simultaneous paired recordings. Consistent with surface charge theory, the post-synaptic current was inhibited by Zn 2+ and this inhibition was relieved by lowering [Ca 2+] o. Nominally divalent-free media produced inversion of HC light responses even though rod light responses remained hyperpolarizing; HC response inversion can be explained by surface charge-mediated shifts in I Ca. In summary, HC light responses modifications induced by low divalent cation solutions can be explained by effects on photoreceptor light responses and membrane surface charge without necessitating Ca 2+-independent neurotransmission. Furthermore, these results suggest that surface charge effects accompanying physiological changing divalent cation levels in the synaptic cleft may provide a means for modulating synaptic output from photoreceptors.

AB - Persistence of horizontal cell (HC) light responses in extracellular solutions containing low Ca 2+ plus divalent cations to block Ca 2+ currents (I Ca) has been attributed to Ca 2+-independent neurotransmission. Using a retinal slice preparation to record both I Ca and light responses, we demonstrate that persistence of HC responses in low [Ca 2+] o can instead be explained by a paradoxical increase of Ca 2+ influx into photoreceptor terminals arising from surface charge-mediated shifts in I Ca activation. Consistent with this explanation, application of Zn 2+ or Ni 2+ caused a hyperpolarizing block of HC light responses that was relieved by lowering [Ca 2+] o. The same concentrations of Zn 2+ and Ni 2+ reduced the amplitude of I Ca at the rod dark potential and this reduction was relieved by a hyperpolarizing shift in voltage dependence induced by lowering [Ca 2+] o. Block of I Ca by Mg 2+, which has weak surface charge effects, was not relieved by low [Ca 2+] o. Recovery of HC responses in low [Ca 2+] o was assisted by enhancement of rod light responses. To bypass light stimulation, OFF bipolar cells were stimulated by steps to -40 mV applied to presynaptic rods during simultaneous paired recordings. Consistent with surface charge theory, the post-synaptic current was inhibited by Zn 2+ and this inhibition was relieved by lowering [Ca 2+] o. Nominally divalent-free media produced inversion of HC light responses even though rod light responses remained hyperpolarizing; HC response inversion can be explained by surface charge-mediated shifts in I Ca. In summary, HC light responses modifications induced by low divalent cation solutions can be explained by effects on photoreceptor light responses and membrane surface charge without necessitating Ca 2+-independent neurotransmission. Furthermore, these results suggest that surface charge effects accompanying physiological changing divalent cation levels in the synaptic cleft may provide a means for modulating synaptic output from photoreceptors.

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