Reducing Extracellular Cl− Suppresses Dihydropyridine-Sensitive Ca2+ Currents and Synaptic Transmission in Amphibian Photoreceptors

Abstract

Thoreson, Wallace B., Ron Nitzan, and Robert F. Miller. Reducing extracellular Cl− suppresses dihydropyridine-sensitive Ca2+ currents and synaptic transmission in amphibian photoreceptors. J. Neurophysiol. 77: 2175–2190, 1997. 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.