May 2007
Volume 48, Issue 13
ARVO Annual Meeting Abstract  |   May 2007
Caffeine: Effect on Glycine Receptors and Synaptic Transmission in Retina
Author Affiliations & Notes
  • L. Duan
    Dept of Neuroscience, State Univ of New York Buffalo, Buffalo, New York
  • M. M. Slaughter
    Dept of Neuroscience, State Univ of New York Buffalo, Buffalo, New York
  • Footnotes
    Commercial Relationships L. Duan, None; M.M. Slaughter, None.
  • Footnotes
    Support NIH Grant EY 014960
Investigative Ophthalmology & Visual Science May 2007, Vol.48, 4592. doi:
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      L. Duan, M. M. Slaughter; Caffeine: Effect on Glycine Receptors and Synaptic Transmission in Retina. Invest. Ophthalmol. Vis. Sci. 2007;48(13):4592.

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      © ARVO (1962-2015); The Authors (2016-present)

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Purpose:: Glycine and GABA are major fast inhibitory transmitters in the retina, and the two receptors share many common features. A previous study showed that caffeine-stimulated calcium release from internal stores suppressed GABAa receptors in retinal ganglion cells (Akopian et al, 1998). We examined whether caffeine would similarly regulate glycine receptors in the ganglion cells.

Methods:: Whole cell voltage-clamp recordings were performed in retinal slices of larval tiger salamanders. Drugs were applied by superfusion and light stimulation employed full field red (660nm) LEDs.

Results:: (A) 10 mM caffeine fully blocked currents produced by exogenously applied 100 µM glycine, but reduced currents induced by 100 µM GABA by less than half. Furthermore, the same caffeine concentration was unable to block current induced by 5 mM glycine. Thus, caffeine seems to be much more effective on glycine receptors, it is dose-dependent, and this inhibition is competitive. When various concentrations of caffeine were tested against 100 µM glycine, the responses could be fit to the Hill equation with an IC50 of 1.6 mM and a Hill coefficient of 1.85. (B) Ryanodine, which can either facilitate (at 10 µM) or block (at 100 µM) calcium release from internal stores, failed to alter 100 µM glycine induced current. Thus internal calcium levels seem to differentially regulate the two major inhibitory neurotransmitters in retina: suppressing GABA but not glycine responses. (C) Since caffeine is also a phosphodiesterase (PDE) inhibitor, we tested several other PDE inhibitors on glycine currents. Theophylline blocked glycinergic spontaneous IPSCs in a dose dependent manner. However, 2 mM theobromine produced only a slight reduction of current produced by 100 µM glycine. (D) When GABA currents were blocked by SR95531, 10 mM caffeine fully blocked glycinergic spontaneous and light-evoked IPSCs. This indicates that synaptic glycine is not saturating. EPSCs were unaffected.

Conclusions:: Caffeine inhibits glycine currents, apparently by direct competitive binding. The Hill coefficient of two suggests that caffeine, like glycine, binds at two sites at each receptor. Unlike GABA receptors, ryanodine receptors and internal calcium stores do not regulate the glycine receptor. Analogs of caffeine also block the glycine receptor, suggesting that the pharmacology of glycine receptors may be similar to that of adenosine receptors.

Keywords: ganglion cells • ion channels • receptors: pharmacology/physiology 

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