Caffeine-Induced Ca2+ Oscillations in Type I Horizontal Cells of the Carp Retina and the Contribution of the Store-Operated Ca2+ Entry Pathway

The mechanisms of release, depletion, and refilling of endoplasmic reticulum (ER) Ca2+ were investigated in type I horizontal cells of the carp retina using a fluo-3-based Ca2+ imaging technique. Exogenous application of caffeine, a ryanodine receptor agonist, induced oscillatory intracellular free Ca2+ concentration ([Ca2+](i)) responses in a duration-and concentration-dependent manner. In Ca2+-free Ringer's solution [Ca2+](i) transients could also be induced by a brief caffeine application, whereas subsequent caffeine application induced no [Ca2+](i) increase, which implied that extracellular Ca2+ was required for ER refilling, confirming the necessity of a Ca2+ influx pathway for ER refilling. Depletion of ER Ca2+ by thapsigargin triggered a Ca2+ influx which could be blocked by the store-operated channel inhibitor 2-APB, which proved he existence of the store-operated Ca2+ entry pathway. Taken together, these results suggested that after being depleted caffeine he ER was replenished by Ca2+ influx via store-operated channels. These results reveal the fine modulation of ling, and the activation of the store-operated Ca2+ entry pathway guarantees the replenishment of the ER so can be ready for response to the subsequent stimulus.