Membrane conductances of mouse cone photoreceptors

Abstract

Vertebrate photoreceptor cells respond to light through a closure of CNG channels located in the outer segment. Multiple voltage-sensitive channels in the photoreceptor inner segment serve to transform and transmit the light-induced outer-segment current response. Despite extensive studies in lower vertebrates, we do not know how these channels produce the photoresponse of mammalian photoreceptors. Here we examined these ionic conductances recorded from single mouse cones in unlabeled, dark-adapted retinal slices. First, we show measurements of the voltage dependence of the light response. After block of voltage-gated Ca2+ channels, the light-dependent current was nearly linear within the physiological range of voltages with constant chord conductance and a reversal potential similar to that previously determined in lower vertebrate photoreceptors. At a dark resting membrane potential of −45 mV, cones maintain a standing Ca2+ current (iCa) between 15 and 20 pA. We characterized the time and voltage dependence of iCa and a calcium-activated anion channel. After constitutive closure of the CNG channels by the nonhydrolysable analogue GTP-γ-S, we observed a light-dependent increase in iCa followed by a Ca2+-activated K+ current, both probably the result of feedback from horizontal cells. We also recorded the hyperpolarization-activated cyclic nucleotide-gated (HCN) conductance (ih) and measured its current-voltage relationship and reversal potential. With small hyperpolarizations, ih activated with a time constant of 25 ms; activation was speeded with larger hyperpolarizations. Finally, we characterized two voltage-gated K+-conductances (iK). Depolarizing steps beginning at −10 mV activated a transient, outwardly rectifying iK blocked by 4-AP and insensitive to TEA. A sustained iK isolated through subtraction was blocked by TEA but was insensitive to 4-AP. The sustained iK had a nearly linear voltage dependence throughout the physiological voltage range of the cone. Together these data constitute the first comprehensive study of the channel conductances of mouse photoreceptors.

Elevated energy requirement of cone photoreceptors

“…To measure the light-dependent inward current of the cone outer segment, we recorded voltage-clamp current responses from both rods and cones in slices of mouse retina, using techniques described previously (SI Appendix ) (4,11,12). We used mice lacking connexin-36 gap junctions (Cx36 −/− ) to avoid any cross-contamination of rod and cone signals (13) and to achieve a more accurate space clamp of the cell.…”

Bayesian inference for biophysical neuron models enables stimulus optimization for retinal neuroprosthetics

“…In their axon terminals, cones express L-type calcium ( ) channels that mediate release of the transmitter glutamate ( Morgans et al, 2005 ; Mansergh et al, 2005 ; Ingram et al, 2020 ). We modeled calcium extrusion purely with calcium pumps ( ) since other mechanisms such as sodium-calcium-exchangers probably only play a minor functional role in cones ( Morgans et al, 1998 ).…”

Functional modulation of phosphodiesterase-6 by calcium in mouse rod photoreceptors

“…The rod outer segment current seems to be independent of the membrane potential in the physiological voltage range in salamander rods 56 . However, a subtle voltage-dependence was discovered in pig rods 57 and in mouse cones 58 . The low Ca 2+ -induced increase in the CNG channel current depolarizes the cell membrane, which could influence the circulating current and LERG-OS responses.…”