Resistance of Retinal Extracellular Space to Ca2+Level Decrease: Implications for the Synaptic Effects of Divalent Cations

1999 ◽  
Vol 82 (1) ◽  
pp. 283-289 ◽  
Author(s):  
Andrey Dmitriev ◽  
Angela Pignatelli ◽  
Marco Piccolino

Ion-sensitive microelectrodes were used to measure the variations of [Ca2+]o induced by application of low Ca2+ media in the superfused eyecup preparation of the Pseudemys turtle. The aim of the experiments was to evaluate the possibility, suggested by previous studies, that in the deep, sclerad, layers of the retina [Ca2+]omay remain high enough to sustain chemical synaptic transmission even after prolonged application of low-Ca2+ saline. It was found that, at depths of 100–200 μm from the vitreal surface, [Ca2+ ]o did not fall below 1 mM even after application for periods of 30–60 min of nominally Ca2+-free media, and it was >0.3 mM after 30-min application of media containing EGTA and with a Ca2+concentration of 1 nM. Previous studies in isolated salamander photoreceptors have shown that a reduction of [Ca2+]o to 0.3–1.0 mM may result in a paradoxical increase of Ca2+ influx into synaptic terminals due to the reduced screening of negative charge on the external face of the plasma membrane. On the basis of these results, the persistence or enhancement of synaptic transmission from photoreceptors to horizontal cells observed in various retinas treated with low-Ca2+ media may be accounted for within the classical Ca2+-dependent theory of synaptic transmission without invoking a Ca2+-independent mechanism.

2009 ◽  
Vol 101 (4) ◽  
pp. 1774-1780 ◽  
Author(s):  
Ziyi Sun ◽  
Dao-Qi Zhang ◽  
Douglas G. McMahon

Hemi-gap-junction (HGJ) channels of retinal horizontal cells (HCs) function as transmembrane ion channels that are modulated by voltage and calcium. As an endogenous retinal neuromodulator, zinc, which is coreleased with glutamate at photoreceptor synapses, plays an important role in shaping visual signals by acting on postsynaptic HCs in vivo. To understand more fully the regulation and function of HC HGJ channels, we examined the effect of Zn2+ on HGJ channel currents in bass retinal HCs. Hemichannel currents elicited by depolarization in Ca2+-free medium and in 1 mM Ca2+ medium were significantly inhibited by extracellular Zn2+. The inhibition by Zn2+ of hemichannel currents was dose dependent with a half-maximum inhibitory concentration of 37 μM. Compared with other divalent cations, Zn2+ exhibited higher inhibitory potency, with the order being Zn2+ > Cd2+ ≈ Co2+ > Ca2+ > Ba2+ > Mg2+. Zn2+ and Ca2+ were found to modulate HGJ channels independently in additivity experiments. Modification of histidine residues with N-bromosuccinimide suppressed the inhibitory action of Zn2+, whereas modification of cysteine residues had no significant effect on Zn2+ inhibition. Taken together, these results suggest that zinc acts on HGJ channels in a calcium-independent way and that histidine residues on the extracellular domain of HGJ channels mediate the inhibitory action of zinc.


2003 ◽  
Vol 89 (2) ◽  
pp. 728-737 ◽  
Author(s):  
Samuel B. Kombian ◽  
Kethireddy V. V. Ananthalakshmi ◽  
Subramanian S. Parvathy ◽  
Wandikayi C. Matowe

Substance P (SP) is an undecapeptide that is co-localized with conventional transmitters in the nucleus accumbens (NAc). Its neurochemical and behavioral effects resemble those of cocaine and amphetamine. How SP accomplishes these effects is not known, partly because its cellular and synaptic effects are not well characterized. Using whole cell and nystatin-perforated patch recording in rat forebrain slices, we show here that SP, an excitatory neuropeptide, depresses evoked excitatory postsynaptic currents (EPSCs) and potentials (EPSPs) in NAc through intermediate neuromodulators. SP caused a partially reversible, dose-dependent decrease in evoked EPSCs. This effect was mimicked by a neurokinin-1 (NK1) receptor-selective agonist, [Sar9, Met (O2)11]-SP and blocked by a NK1 receptor-selective antagonist, L 732 138. Both the SP- and [Sar9, Met (O2)11]-SP-induced synaptic depressions were accompanied by increases in paired pulse ratio (PPR), effects that were also blocked by L 732 138. In contrast to its effect on PPR, SP did not produce significant changes in the holding current, input resistance, EPSC decay rate (τ), and steady-state I-V curves of the recorded cells. The SP-induced synaptic depressions were prevented by dopamine receptor blockade using SCH23390 and haloperidol, but not by sulpiride. In addition, the SP-induced synaptic depression was blocked by an adenosine A1 receptor blocker 8-cyclopentyltheophylline (8-CPT) but not the N-methyl-d-aspartate (NMDA) receptor antagonist d-APV. These data show that SP, by activating presynaptic NK1 receptors, depresses excitatory synaptic transmission indirectly by enhancing extracellular dopamine and adenosine levels. Since the cellular and synaptic effects of SP resemble those of cocaine and amphetamine, it may serve as an endogenous psychogenic peptide.


1983 ◽  
Vol 41 (3) ◽  
pp. 764-771 ◽  
Author(s):  
Robert E. Anderson ◽  
Maureen B. Maude ◽  
Paula A. Kelleher ◽  
Mary E. Rayborn ◽  
Joe G. Hollyfield

1986 ◽  
Vol 250 (6) ◽  
pp. E702-E710 ◽  
Author(s):  
V. Baracos ◽  
R. E. Greenberg ◽  
A. L. Goldberg

When rat muscles were incubated in Ca2+-free media, their rates of protein break-down were significantly lower than in complete medium (2.58 mM Ca2+). Dantrolene and 3,4,5-trimethoxybenzoic acid 8-(diethylamino)octyl ester, inhibitors of Ca2+ release from the sarcoplasmic reticulum, also reduced muscle proteolysis. When Ca2+ was added (up to 5.16 mM), proteolysis increased progressively up to 70% in the intact soleus and extensor digitorum longus muscles and up to 300% in the cut diaphragm preparation. Addition of Ca2+ did not affect the muscles' ATP or phosphocreatine content and increased protein synthesis slightly or not at all. Sr2+, Ba2+, and Mn2+ also increased proteolysis, but were less effective than Ca2+. Mg2+ inhibited the enhancement of proteolysis by Ca2+. This stimulation by Ca2+ was not affected by inhibitors of voltage-dependent Ca2+ channels, calmodulin, metalloendoproteases, microfilament or microtubule formation, or mersalyl. High Ca2+ levels also increased prostaglandin (PG) E2 production, although a rise in PGE2 did not appear essential for the increased proteolysis. The proteolysis induced by Ca2+ was prevented in muscles treated with Ep-475 or leupeptin. By contrast, these inhibitors of thiol proteases did not affect protein breakdown in Ca2+-free medium. Thus extracellular Ca2+ activates and Mg2+ inhibits a proteolytic pathway involving thiol proteases.


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