Horizontal cell feedback regulates calcium currents and intracellular calcium levels in rod photoreceptors of salamander and mouse retina (original) (raw)
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F1000 - Post-publication peer review of the biomedical literature, 2000
Retinal horizontal cells (HCs) provide negative feedback to cones, but, largely because annular illumination fails to evoke a depolarizing response in rods, it is widely believed that there is no feedback from HCs to rods. However, feedback from HCs to cones involves small changes in the calcium current (I Ca) that do not always generate detectable depolarizing responses. We therefore recorded I Ca directly from rods to test whether they were modulated by feedback from HCs. To circumvent problems presented by overlapping receptive fields of HCs and rods, we manipulated the membrane potential of voltage-clamped HCs while simultaneously recording from rods in a salamander retinal slice preparation. Like HC feedback in cones, hyperpolarizing HCs from Ϫ14 to Ϫ54, Ϫ84, and Ϫ104 mV increased the amplitude of I Ca recorded from synaptically connected rods and caused hyperpolarizing shifts in I Ca voltage dependence. These effects were blocked by supplementing the bicarbonate-buffered saline solution with HEPES. In rods lacking light-responsive outer segments, hyperpolarizing neighboring HCs with light caused a negative activation shift and increased the amplitude of I Ca. These changes in I Ca were blocked by HEPES and by inhibiting HC light responses with a glutamate antagonist, indicating that they were caused by HC feedback. These results show that rods, like cones, receive negative feedback from HCs that regulates the amplitude and voltage dependence of I Ca. HC-to-rod feedback counters light-evoked decreases in synaptic output and thus shapes the transmission of rod responses to downstream visual neurons.
Feedback from Horizontal Cells to Rod Photoreceptors in Vertebrate Retina
Journal of Neuroscience, 2008
Retinal horizontal cells (HCs) provide negative feedback to cones, but, largely because annular illumination fails to evoke a depolarizing response in rods, it is widely believed that there is no feedback from HCs to rods. However, feedback from HCs to cones involves small changes in the calcium current (I Ca) that do not always generate detectable depolarizing responses. We therefore recorded I Ca directly from rods to test whether they were modulated by feedback from HCs. To circumvent problems presented by overlapping receptive fields of HCs and rods, we manipulated the membrane potential of voltage-clamped HCs while simultaneously recording from rods in a salamander retinal slice preparation. Like HC feedback in cones, hyperpolarizing HCs from Ϫ14 to Ϫ54, Ϫ84, and Ϫ104 mV increased the amplitude of I Ca recorded from synaptically connected rods and caused hyperpolarizing shifts in I Ca voltage dependence. These effects were blocked by supplementing the bicarbonate-buffered saline solution with HEPES. In rods lacking light-responsive outer segments, hyperpolarizing neighboring HCs with light caused a negative activation shift and increased the amplitude of I Ca. These changes in I Ca were blocked by HEPES and by inhibiting HC light responses with a glutamate antagonist, indicating that they were caused by HC feedback. These results show that rods, like cones, receive negative feedback from HCs that regulates the amplitude and voltage dependence of I Ca. HC-to-rod feedback counters light-evoked decreases in synaptic output and thus shapes the transmission of rod responses to downstream visual neurons.
Brain Research, 1997
We examined the contribution of two intrinsic voltage-dependent calcium channels to the light-evoked responses of a non-spiking Ž . retinal neuron, the horizontal cell HC . HC's isolated from the Xenopus retina were studied by the whole cell version of the patch clamp. In a mixture of agents which suppressed Na-and K-dependent currents, we identified a transient, low voltage-activated Ca current 2q 2q Ž . suppressed by Ba and blocked by Ni T-type and a sustained, high voltage-activated, dihydropyridine-sensitive Ca current that was 2q Ž . enhanced by Ba L-type . We made simultaneous intracellular recordings from rods and HC's in the intact, dark-adapted Xenopus retina. Under certain stimulus conditions, transient oscillations appeared in HC responses but were absent in rod light-evoked waveforms.
European Journal of Neuroscience, 2002
L-type Ca 2+ currents (I Ca) in rod photoreceptors exhibit Ca 2+-dependent inactivation. Perforated-patch whole-cell recordings were obtained from isolated rods of the tiger salamander using 1.8 mM Ca 2+ in the bathing medium to determine the extent of Ca 2+dependent inactivation of I Ca with physiological [Ca 2+ ] and endogenous buffering. I Ca was measured with voltage ramps applied before and after 5-s steps to ±40, ±30, ±20, or ±10 mV. Long depolarizing steps in isolated rods produced inactivation of I Ca ranging from 15% at ±40 mV to > 80% at ±10 mV. Because, in addition to Ca 2+-dependent inactivation, depletion of synaptic cleft Ca 2+ accompanying activation of I Ca can reduce presynaptic I Ca at calycal synapses, we investigated whether a similar mechanism worked at the invaginating rod synapse. Rods from retinal slices with intact synapses were compared with isolated rods in which synaptic cleft depletion is absent. I Ca was more strongly depressed by depolarization of rods in retinal slices, with I Ca reduced by 47% following voltage steps to ±40 mV. The depression of currents by depolarization was also greater for rods from retinal slices than isolated rods when Ca 2+ was replaced with Ba 2+ to reduce Ca 2+-dependent inactivation. The stronger depolarization-evoked inhibition of I Ca in retinal slices compared to isolated rods probably re¯ects depletion of synaptic cleft Ca 2+ arising from sustained Ca 2+ in¯ux. Inactivation of I Ca exhibited slow onset and recovery. These ®ndings suggest that Ca 2+dependent inactivation and depletion of synaptic cleft Ca 2+ may combine to regulate I Ca in response to light-evoked changes in rod membrane potential.
Physiological Reports, 2015
Differences in synaptic transmission between rod and cone photoreceptors contribute to different response kinetics in rod-versus cone-dominated visual pathways. We examined Ca 2+ dynamics in synaptic terminals of tiger salamander photoreceptors under conditions that mimicked endogenous buffering to determine the influence on kinetically and mechanistically distinct components of synaptic transmission. Measurements of I Cl(Ca) confirmed that endogenous Ca 2+ buffering is equivalent to~0.05 mmol/L EGTA in rod and cone terminals. Confocal imaging showed that with such buffering, depolarization stimulated large, spatially unconstrained [Ca 2+ ] increases that spread throughout photoreceptor terminals. We calculated immediately releasable pool (IRP) size and release efficiency in rods by deconvolving excitatory postsynaptic currents and presynaptic Ca 2+ currents. Peak efficiency of~0.2 vesicles/channel was similar to that of cones (~0.3 vesicles/channel). Efficiency in both cell types was not significantly affected by using weak endogenous Ca 2+ buffering. However, weak Ca 2+ buffering speeded Ca 2+ /calmodulin (CaM)-dependent replenishment of vesicles to ribbons in both rods and cones, thereby enhancing sustained release. In rods, weak Ca 2+ buffering also amplified sustained release by enhancing CICR and CICR-stimulated release of vesicles at nonribbon sites. By contrast, elevating [Ca 2+ ] at nonribbon sites in cones with weak Ca 2+ buffering and by inhibiting Ca 2+ extrusion did not trigger additional release, consistent with the notion that exocytosis from cones occurs exclusively at ribbons. The presence of weak endogenous Ca 2+ buffering in rods and cones facilitates slow, sustained exocytosis by enhancing Ca 2+ /CaMdependent replenishment of ribbons in both rods and cones and by stimulating nonribbon release triggered by CICR in rods.
Calcium homeostasis in the outer segments of retinal rods from the tiger salamander
The Journal of Physiology, 1992
The processes regulating intracellular calcium in the outer segments of salamander rods have been investigated. The main preparation used was the isolated rod loaded with the Ca2+-sensitive photoprotein aequorin, from which outer segment membrane current and free [Ca2+]i could be recorded simultaneously. Two other preparations were also used: outer segment membrane current was recorded from intact, isolated rods using a suction pipette, and from detached outer segments using a whole-cell pipette. 2. Measurements of free intracellular [Ca2+] in Ringer solution were obtained from two aequorin-loaded rods. Mean [Ca2+]i in darkness was 0-41 /M, and after a bright flash [Ca21]i fell to below detectable levels (< 0 3 UM). No release of intracellular Ca2+ by a bright flash of light could be detected (< 0-2 #M). 3. Application of the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX) caused an increase in the size of the light-sensitive current and a rise in [Ca21]i, but application of IBMX either when the light-sensitive channels had been closed by a bright light or in the absence of external Ca2+ caused no detectable rise in [Ca2+]i. It is concluded that IBMX increases [Ca2+]i by opening light-sensitive channels, and does not release Ca2+ from stores within the outer segment. 4. Removal of external Na+ caused a rise in [Ca2+]i to around 2 #tM and completely suppressed the light-sensitive current. 5. The Na+-Ca2+, K+ exchange current in aequorin-loaded rods was activated in first-order manner by internal free calcium, with a mean Michaelis constant, KCa' of 1-61uM. 6. The K~a of the Na+-Ca2+, K+ exchange was increased by elevating internal [Na+]. 7. The Michaelis relation between [Ca2+]i and the activity of the Na+-Ca2+, K+ exchange was used to calculate the change in [Ca2+]i occurring during the response to a bright light. In aequorin-loaded rods in Ringer solution the mean change in free
Chloride currents in cones modify feedback from horizontal cells to cones in goldfish retina
The Journal of Physiology, 2012
• The GABAergic pathway modulates feedback between retinal horizontal cells (HCs) and cone photoreceptors, but is not mediating negative feedback, as previously hypothesized. • Opening of GABA-gated chloride channels in cone photoreceptors reduces the amplitude of feedback responses generated by HCs. • Activation of a different presynaptic chloride current, the calcium-dependent chloride current, in individual cones has a similar effect on feedback as application of GABA. • Modulation of the strength of feedback from HCs seems to be a general consequence of activation of presynaptic chloride currents in cones. • This puts the functional role of these currents in a new perspective; GABA acts as a slow and global neuromodulator enhancing feedback in the light-and attenuating feedback in the dark-adapted retina, whereas the calcium-dependent chloride current modulates feedback fast and locally to tune the size of feedback to local light conditions.
Proceedings of the National Academy of Sciences, 1996
According to the classical calcium hypothesis of synaptic transmission, the release of neurotransmitter from presynaptic terminals occurs through an exocytotic process triggered by depolarization-induced presynaptic calcium influx. However, evidence has been accumulating in the last two decades indicating that, in many preparations, synaptic transmitter release can persist or even increase when calcium is omitted from the perfusing saline, leading to the notion of a "calcium-independent release" mechanism. Our study shows that the enhancement of synaptic transmission between photoreceptors and horizontal cells of the vertebrate retina induced by low-calcium media is caused by an increase of calcium influx into presynaptic terminals. This paradoxical effect is accounted for by modifications of surface potential on the photoreceptor membrane. Since lowering extracellular calcium concentration may likewise enhance calcium influx into other nerve cells, other experimental obse...
Journal of General Physiology, 1977
effects of altering extracellular Ca 2+ levels on the electrical and adaptive properties of toad rods have been examined. The retina was continually superfused in control (1.6 mM Ca 2+) or test Ringer's solutions, and rod electrical activity was recorded intracellularly. Low-calcium Ringer's 00-9 M Ca ~+) superfused for up to 6 min caused a substantial depolarization of the resting membrane potential, an increase in light-evoked response amplitudes, and a change in the waveform of the Light-evoked responses. High Ca ~+ Ringer's (3.2 mM) hyperpolarized the cell membrane and decreased response amplitudes. However, under conditions of either low or high Ca ~+ superfusion for up to 6 min, in both dark-adapted and partially light-adapted states, receptor sensitivity was virtually unaffected; i.e., the V-log I curve for the receptor potential was always located on the intensity scale at a position predicted by the prevailing light level, not by Ca 2+ concentration. Thus, we speculate that cytosol Ca ~+ concentration is capable of regulating membrane potential levels and light-evoked response amplitudes, but not the major component of rod sensitivity. Low Ca ~+ Ringer's also shortened the period of receptor response saturation after a bright but nonbleaching light flash, hence accelerating the onset of both membrane potential and sensitivity recovery during dark adaptation. Exposure of the retina to low Ca 2+ (10-9 M) Ringer's for long periods (7-15 min) caused dark-adapted rods to lose responsiveness. Response amplitudes gradually decreased, and the rods became desensitized. These severe conditions of low Ca ~+ caused changes in the dark-adapted rod that mimic those observed in rods during light adaptation. We suggest that loss of receptor sensitivity during prolonged exposure to low Ca 2+ Ringer's results from a decrease of intraceilular (intradisk) stores of Ca2+; i.e., less Ca ~+ is thereby released per quantum catch.
Voltage-Gated Channels and Calcium Homeostasis in Mammalian Rod Photoreceptors
Journal of …, 2005
Recent reports on rod photoreceptor neuroprotection by Ca 2+ channel blockers have pointed out the need to assess the effect of these blockers on mammalian rods. However, in mammals, rod electrophysiological characterization has been hampered by the small size of these photoreceptors which were instead extensively studied in non-mammalian vertebrates.