The effects of bicarbonate on the aberrant photon response in murine rod photoreceptors

Retinal rod photoreceptors generate reproducible quantal responses enabling them to "count" single photons. Interestingly, in mammalian rods, one photoisomerization in several hundred elicits an aberrant response that is larger than normal and persists for a variable period lasting up to tens of seconds. Although rare, aberrant responses influence signaling because many rods converge onto downstream neurons and because "normal" and aberrant single photon responses temporally summate in steady light. Bicarbonate increases the normal photon response and the maximal response of rods, but its effect on the aberrant responses is not known. To find out, we used a fully space-resolved, biophysical model of visual transduction in the murine rod and corroborated the results with ex vivo electroretinogram (ERG) recordings. In our simulations, the increased circulating current with bicarbonate raised [Ca2+]in, which suppressed the shutoff of photoexcited rhodopsin during the normal single photon response but not during the aberrant response. Consequently, the normal single photon response was enlarged to a greater extent than the aberrant response. In ERG recordings, aberrant responses gave rise to a long-lived tail in the bright flash response, that was used to assess how they were affected by bicarbonate. Indeed, the increase in aberrant response amplitude with bicarbonate was less than that for the normal photon response, consistent with modeling. In simulations, the accumulation of aberrant responses produced a slow, secondary rise in the step response to subsaturating intensities. But in the ERG, the secondary rise seemed to disappear with bicarbonate. By boosting normal photon responses and the maximal response, bicarbonate elicited a droop in the step response due to light adaptation (not included in the model) that was more prominent and appeared at lower intensities. Because bicarbonate also reduced the relative contribution of the aberrant response component, the droop merged with and obscured the secondary rise.