Conditioning hyperpolarization reveals a property of the light-sensitive current in photoreceptors that is modified by cGMP and EGTA.

In the dark, an ionic current flows into the outer segments of retinal rods. The absorption of photons by rhodopsin leads to a graded suppression or inactivation of this inward 'light-sensitive' current. The present study shows that following a conditioning hyperpolarization of the rod membrane in the dark, there was a transient increase in total inward current which could no longer be completely suppressed or inactivated by a bright light. The increased inward current following a hyperpolarization had the same reversal potential as the normal inward current but was apparently less sensitive to light. Thus the chain of events between light stimulation and the subsequent membrane current response can be influenced by voltage. Previously, it has been shown that the light-sensitive current is modulated by cGMP and Ca2+, both of which have been proposed as internal messengers that link the absorption of photons to the change in inward membrane current. In the present study, intracellular injection of cGMP or EGTA produced an additional increase in inward current following a conditioning hyperpolarization. On the other hand, these substances antagonized the effect of voltage by permitting complete inactivation of the total inward current by light after a hyperpolarizing step. These results indicate that cyclic nucleotides and calcium can modify the inactivation of an ionic current following a conditioning hyperpolarization. A simple model suggests that these findings are consistent with the notion that this inward conductance in rods has two open states, one sensitive to light and the other insensitive. cGMP or low Ca2+ appears to favor the open state that can be inactivated by light.