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.
Thoreson
W B
WB
Department of Ophthalmology, University of Nebraska Medical Center, Omaha 68198-5540, USA.
Nitzan
R
R
Miller
R F
RF
D000557:Ambystoma; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002712:Chlorides / Q000502:physiology*; D004095:Dihydropyridines / Q000494:pharmacology*; D005071:Evoked Potentials / Q000528:radiation effects; D018698:Glutamic Acid / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D008027:Light; D009337:Necturus; D009474:Neurons / Q000187:drug effects* / Q000528:radiation effects; D010786:Photoreceptor Cells / Q000378:metabolism / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology*
D002121:Calcium Channel Blockers; D002712:Chlorides; D004095:Dihydropyridines; D018698:Glutamic Acid; C038806:1,4-dihydropyridine