Intracellular calcium reduces light-induced excitatory post-synaptic responses in salamander retinal ganglion cells.
The whole-cell patch clamp technique was used to study the effect of intracellular Ca2+ on light-evoked EPSCs in on-off ganglion cells in salamander retinal slices. Both AMPA and NMDA receptors contributed to the light-evoked responses. In the presence of strychnine and picrotoxin, ganglion cells responded to light onset and offset with transient inward currents at -70 mV. These currents were reduced by 35 +/- 3 % when the light stimulus was preceded by a depolarizing step from -70 to 0 mV. The inhibitory effect of depolarization on light-evoked EPSCs was strongly reduced in the presence of 10 mM BAPTA. The degree of EPSC inhibition by the prepulse holding potential followed the current-voltage relationship of the Ca2+ current found in the ganglion cell. In the presence of the NMDA receptor antagonist AP-7, glutamate-dependent current was nearly abolished when high Ca2+ was substituted for high Na+ solution. The release of Ca2+ from internal stores by caffeine or inositol trisphosphate reduced the EPSCs by 36 +/- 5 and 38 +/- 11 %, respectively, and abolished the inhibitory effect of depolarization. The inhibitory effect of depolarization on EPSCs was reduced 5-fold in the presence of AP-7, but was not reduced by the AMPA receptor antagonist CNQX. Neither inhibition of Ca2+-calmodulin-dependent enzymes, nor inhibition of protein kinase A or C had any significant effect on the depolarization-induced inhibition of EPSCs. Our data suggest that elevation of [Ca2+]i, through voltage-gated channels or by release from intracellular stores, reduced primarily the NMDA component of the light-evoked EPSCs.
Department of Ophthalmology, New York University School of Medicine, New York, NY 10016, USA. aa3@nyu.edu
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Akopian
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Witkovsky
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000494:pharmacology; D015763:2-Amino-5-phosphonovalerate / Q000031:analogs & derivatives / Q000494:pharmacology; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000557:Ambystoma; D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D002614:Chelating Agents / Q000494:pharmacology; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D066298:In Vitro Techniques; D007473:Ion Channels / Q000378:metabolism*; D008027:Light; D018408:Patch-Clamp Techniques; D047428:Protein Kinase Inhibitors; D018091:Receptors, AMPA / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D012165:Retinal Ganglion Cells / Q000187:drug effects / Q000502:physiology*; D012964:Sodium / Q000378:metabolism
D000697:Central Nervous System Stimulants; D002614:Chelating Agents; D004791:Enzyme Inhibitors; D018691:Excitatory Amino Acid Antagonists; D007473:Ion Channels; D047428:Protein Kinase Inhibitors; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; D002110:Caffeine; D004533:Egtazic Acid; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D015763:2-Amino-5-phosphonovalerate; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D012964:Sodium; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; C031231:2-amino-7-phosphonoheptanoic acid; D002118:Calcium