Intracellular calcium release resulting from mGluR1 receptor activation modulates GABA_A currents in wide‐field retinal amacrine cells: a study with caffeine

Abstract

The modulatory action of calcium (Ca2+) released from intracellular stores on GABAA receptor-mediated current was investigated in wide-field amacrine cells isolated from the teleost, Morone chrysops, retina. Caffeine, ryanodine or inositol 1,4,5-triphosphate (IP3) markedly inhibited the GABAA current by elevating [Ca2+]i. The inhibition resulted from the activation of a Ca2+--> Ca2+/calmodulin --> calcineurin cascade. Long (>12 s) exposure to glutamate mimicked the caffeine effect, i.e. it inhibited the GABAA current by elevating [Ca2+]i through mGluR1 receptor activation and consequent IP3 generation. This pathway provides a 'timed' disinhibitory mechanism to potentiate excitatory postsynaptic potentials in wide-field amacrine cells. It occurs as a result of the suppression of GABA-mediated conductances as a function of the duration of presynaptic excitatory input activity. This is much like some forms of long-term potentiation in the central nervous system. In a local retinal circuit this will selectively accentuate particular excitatory inputs to the wide-field amacrine cell. Similar to other neural systems, we suggest that activity-dependent postsynaptic disinhibition is an important feature of the signal processing in the inner retina.

Activation of group I metabotropic glutamate receptors regulates the excitability of rat retinal ganglion cells by suppressing Kir and I h

“…Secondly, immunostaining and electron microscopic studies in rat retina have shown that mGluR1 was present in the AC processes postsynaptic to axon terminal of OFFcone, ON-cone and rod BCs (Koulen et al 1997). On the other hand, it was reported that activation of mGluR1 on GABAergic ACs increased GABA release (Vigh and Lasater 2003). Considering the fact that elevated GABA level may increase inhibitory inputs to RGCs and decrease RGC excitability, inhibition of mGluR I should attenuate inhibitory inputs to RGCs, thus increasing RGC firing.…”

Modulation by Brain Natriuretic Peptide of GABA Receptors on Rat Retinal ON-Type Bipolar Cells

“…That CaM mediates suppression of GABA A currents caused by elevated levels of [Ca 2ϩ ] i has been shown in turtle ganglion cells (Akopian et al, 1998) and white bass amacrine cells (Vigh and Lasater, 2003). CaM also mediates the suppression effect of elevated levels of [Ca 2ϩ ] i on the function of GABA B receptors in tiger salamander retina (Shen and Slaughter, 1999).…”

“…In the retina, for instance, activation of mGluR5 enhances GABA A currents in cultured chick amacrine cells, an effect that is both Ca 2ϩ and PKC dependent (Hoffpauir and Gleason, 2002). Calcium release from intracellular stores caused by activation of mGluR1, on the other hand, suppresses GABA A currents through the IP 3 pathway in white bass wide-field amacrine cells (Vigh and Lasater, 2003). In ONtype BCs, glutamate released from rods acts on the glutamate receptor mGluR6 (Nawy, 2000), and activation of this receptor is supposed to reduce intracellular cGMP levels by stimulating PDE, although there is recent evidence suggesting that a change in cGMP may be not the signal for the closure of nonselective cation channels of ON-type BCs in tiger salamander (Nawy, 1999).…”

Metabotropic Glutamate 1 Receptor: Current Concepts and Perspectives

“…This modulation has been shown in cerebellar PCs in response to the combined activation of mGlu1 and TrkB receptors (see section VI.B.6) and in retinal amacrine cells, in which stimulation of group I mGlu receptors inhibits GABA A currents through a mechanism that involves an increase in intracellular Ca 2ϩ , which triggers a calmodulin/calcineurin cascade (Vigh and Lasater, 2003). How-546 ever, it is not known whether the latter process is mediated by mGlu1 or mGlu5 receptors (Vigh and Lasater, 2003).…”