Electrical and adaptive properties of rod photoreceptors in bufo marinus : II. effects of cyclic nucleotides and prostaglandins

Abstract

Substances known to alter cyclic nucleotide levels in cells were applied to the isolated toad retina and effects on rod electrical and adaptive behavior were studied. The retina was continually superfused in control Ringer’s or Ringer’s containing one or a combination of drugs, and rod activity was recorded intracellularly. Superfusion with cGMP, Bu2cGMP, isobutylmethylxanthine (IBMX; a phosphodiesterase inhibitor), or PGF2a (a prostaglandin) caused effects in rods that closely match those observed when extracellular Ca2+ levels were lowered. For example, short exposures (up to 6 min) of the retina to these substances caused depolarization of the membrane potential, increase in response amplitudes, and some changes in waveform; but under dark-adapted or partially light-adapted conditions receptor sensitivity was virtually unaffected. That is, the position of the V-log I curve on the intensity axis was determined by the prevailing light level, not by drug level. These drugs, like lowered extracellular Ca2+, also decreased the period of receptor saturation after a bright-adapting flash, resulting in an acceleration of the onset of membrane and sensitivity recovery during dark adaptation. Long-term (6-15 min) exposure of a dark-adapted retina to 5 mM IBMX or a combination of IBMX and cGMP caused a loss of response amplitude and a desensitization of the rods that was similar to that observed in rods after a longterm low Ca2+ (10-9 M) treatment. Application of high (3.2 mM) Ca2+ to the retina blocked the effects of applied Bu2cGMP. PGE, superfusion mimicked the effects of increasing extracellular Ca2+. The results show that increased cGMP and lowered Ca2+ produce similar alterations in the electrical activity of rods. These findings suggest that Ca2+ and cGMP are interrelated messengers. We speculate that low Ca2+ may lead to increased intracellular cGMP, and/or that applied cGMP may lower cytosol Ca2+, perhaps by stimulating Ca2+-ATPase pumps in the outer segment. © 1977, Rockefeller University Press., All rights reserved.