Caffeine-sensitive calcium stores regulate synaptic transmission from retinal rod photoreceptors

J Neurosci. 1999 Sep 1;19(17):7249-61. doi: 10.1523/JNEUROSCI.19-17-07249.1999.

Abstract

We investigated the role of caffeine-sensitive intracellular stores in regulating intracellular calcium ([Ca(2+)](i)) and glutamatergic synaptic transmission from rod photoreceptors. Caffeine transiently elevated and then markedly depressed [Ca(2+)](i) to below prestimulus levels in rod inner segments and synaptic terminals. Concomitant with the depression was a reduction of glutamate release and a hyperpolarization of horizontal cells, neurons postsynaptic to rods. Caffeine did not affect the rods' membrane potentials indicating that caffeine likely acted via some mechanism(s) other than a voltage-dependent deactivation of the calcium channels. Most of caffeine's depressive action on [Ca(2+)](i), on glutamate release, and on I(Ca) in rods can be attributed to calcium release from stores: (1) caffeine's actions on [Ca(2+)](i) and I(Ca) were reduced by intracellular BAPTA and barium substitution for calcium, (2) other nonxanthine store-releasing compounds, such as thymol and chlorocresol, also depressed [Ca(2+)](i), and (3) the magnitude of [Ca(2+)](i) depression depended on basal [Ca(2+)](i) before caffeine. We propose that caffeine-released calcium reduces I(Ca) in rods by an as yet unidentified intracellular signaling mechanism. To account for the depression of [Ca(2+)](i) below rest levels and the increased fall rate of [Ca(2+)](i) with higher basal calcium, we also propose that caffeine-evoked calcium release from stores activates a calcium transporter that, via sequestration into stores or extrusion, lowers [Ca(2+)](i) and suppresses glutamate release. The effects of store-released calcium reported here operate at physiological calcium concentrations, supporting a role in regulating synaptic signaling in vivo.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Ambystoma
  • Animals
  • Barium / pharmacology
  • Caffeine / pharmacology*
  • Calcium / physiology*
  • Calcium Channels / physiology
  • Chelating Agents / pharmacology
  • Cresols / pharmacology
  • Egtazic Acid / analogs & derivatives
  • Egtazic Acid / pharmacology
  • Electrophysiology
  • In Vitro Techniques
  • Kinetics
  • Models, Neurological
  • Presynaptic Terminals / drug effects
  • Presynaptic Terminals / physiology*
  • Retinal Rod Photoreceptor Cells / drug effects
  • Retinal Rod Photoreceptor Cells / physiology*
  • Ryanodine / pharmacology
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology*
  • Thymol / pharmacology
  • Xenopus laevis

Substances

  • Calcium Channels
  • Chelating Agents
  • Cresols
  • Ryanodine
  • Barium
  • chlorocresol
  • Caffeine
  • Thymol
  • Egtazic Acid
  • 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid
  • Calcium