Abstract
Purpose: :
Taurine is the most abundant free amino acid in the retina but while taurine has been implicated in neurotransmission and neuromodulation, its specific sites of action are not fully understood. Immunoreactive patterns in salamander retinas show that taurine labeling is present in rods, a few cones and displaced Off-bipolar cells. Ionotropic taurine current is sensitive to both glycine receptor and GABA receptor antagonists, however little study has been done on strychnine- and picrotoxin- insensitive metabotropic taurine regulation. The results from this study show the metabotroic taurine effect regulates K+ channels preferentially in OFF-bipolar cells.
Methods: :
Whole-cell patch clamp recordings were applied in larval tiger salamander retinal cells. The regulation of the delayed-rectifier K+ current by taurine was studied in an inhibitory cocktail solution containing TTX, Cd2+, picrotoxin and strychnine to block voltage-gated Ca2+ and Na+ channels, as well as Cl- permeable ionotropic channels. Isolated retinal neurons were studied to determine the intracellular mechanism of regulation while slice preparation was used to determine cell subtype specific regulation and differentiate taurine effects from those of glycine.
Results: :
The strychnine- and picrotoxin-insensitive effects of taurine caused an enhancement of the outward K+ currents in OFF-bipolar cells, but not in ON-bipolar cells. The enhancement acted on the delayed-rectifier K+ currents of the Kv1.3 subtype through a PKC-dependent pathway and was insensitive to GABAB receptor antagonists. In contrast, glycine caused a suppression of K+ current in ON-bipolar cells and had little effect in OFF-bipolar cells through a PKA-dependent pathway. A potential site for the action of taurine was determined using specific serotonin receptor antagonists.
Conclusions: :
Our results provide the evidence that at physiological concentrations taurine may have a neuromodulatory role in the OFF-bipolar cells via serotonin-sensitive receptors and a PKC intracellular pathway. The metabotropic taurine effect in the retinal neurons could have an important implication for the actions of taurine in central brain in which taurine has been known to be beneficial for improving mental health, as well as learning and memory.
Keywords: taurine • second messengers • retina: distal (photoreceptors, horizontal cells, bipolar cells)