Reducing extracellular Cl^- suppresses dihydropyridine-sensitive Ca²⁺ currents and synaptic transmission in amphibian photoreceptors

A reduction in extracellular chloride suppresses light-evoked currents of second-order retinal neurons (bipolar and horizontal cells) by reducing release of glutamate from photoreceptors. The underlying mechanisms responsible for this action of reduced extracellular Cl^- were studied with a combination of electrophysiological recordings from single neurons in a retinal slice preparation and image analyses of intracellular Ca²⁺ (Fura- 2) and pH [2',7'-bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein, acetoxymethyl ester] in dissociated photoreceptors. The results show that reducing extracellular Cl^- suppresses a dihydropyridine (DHP)-sensitive Ca²⁺ current (I(Ca)) in photoreceptors. It is proposed that suppression of I(Ca) results in suppression of photoreceptor neurotransmission. The suppressive effect of low Cl^- on I(Ca) is not due to antagonism by the substituting anion nor is it mediated by changes in extracellular or intracellular pH. We conclude that normal extracellular levels of Cl^- are important for maintenance of the voltage-gated Ca²⁺ channels that support neurotransmission from photoreceptors. Several ideas are presented about the mechanisms by which Cl^- supports photoreceptor neurotransmission and the possibility that modulations of Cl^- might play a physiological role in the regulation of Ca²⁺ channels in photoreceptors and, hence, photoreceptor function.