The Journal of general physiologyApr 4, 2002

Voltage sensitivity of ion flow in light-detecting cells is tuned for their function in rods and cones

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Updated Mar 25, 2026

Abstract

Pf, the fraction of current carried by Ca(2+), is independent of membrane voltage between -65 and -25 mV in both rod and cone photoreceptors.

The kinetics of photocurrent in retinal photoreceptors does not vary with changes in membrane voltage over the tested range.
Pf is larger in cones than in rods, indicating a difference in the ionic current carried by Ca(2+) between these cell types.
The observed independence of Pf from membrane voltage suggests that light, rather than voltage, controls the kinetics of the phototransduction current.
A rate theory model of ion permeation was developed, proposing two ion binding sites within the channel's permeation pore to explain the findings.
Model simulations accurately represent experimental photocurrents and align with the voltage-independence of Pf, supporting optimized channel function.

Simplified

The kinetics of the photocurrent in both rod and cone retinal photoreceptors are independent of membrane voltage over the physiological range (-30 to -65 mV). This is surprising since the photocurrent time course is regulated by the influx of Ca(2+) through cGMP-gated ion channels (CNG) and the force driving this flux changes with membrane voltage. To understand this paradigm, we measured Pf, the fraction of the cyclic nucleotide-gated current specifically carried by Ca(2+) in intact, isolated photoreceptors. To measure Pf we activated CNG channels by suddenly increasing free 8-Br-cGMP in the cytoplasm of rods or cones loaded with a caged ester of the cyclic nucleotide. Simultaneous with the uncaging flash, we measured the cyclic nucleotide-dependent changes in membrane current and fluorescence of the Ca(2+) binding dye, Fura-2, also loaded into the cells. We determined Pf under physiological solutions at various holding membrane voltages between -65 and -25 mV. Pf is larger in cones than in rods, but in both photoreceptor types its value is independent of membrane voltage over the range tested. This biophysical feature of the CNG channels offers a functional advantage since it insures that the kinetics of the phototransduction current are controlled by light, and not by membrane voltage. To explain our observation, we developed a rate theory model of ion permeation through CNG channels that assumes the existence of two ion binding sites within the permeation pore. To assign values to the kinetic rates in the model, we measured experimental I-V curves in membrane patches of rods and cones over the voltage range -90 to 90 mV in the presence of simple biionic solutions at different concentrations. We optimized the fit between simulated and experimental data. Model simulations describe well experimental photocurrents measured under physiological solutions in intact cones and are consistent with the voltage-independence of Pf, a feature that is optimized for the function of the channel in photoreceptors.

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Voltage sensitivity of ion flow in light-detecting cells is tuned for their function in rods and cones

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