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1.
The interstitial voltages, currents, and resistances of the receptor layer of the isolated rat retina have been investigated with arrays of micropipette electrodes inserted under direct visual observation by infrared microscopy. In darkness a steady current flows inward through the plasma membrane of the rod outer segments. It is balanced by equal outward current distributed along the remainder of each rod. Flashes of light produce a photocurrent which transiently reduces the dark current with a waveform resembling the PII and a-wave components of the electroretinogram. The photocurrent is produced by a local action of light within 12 μm of its point of absorption in the outer segments. The quantum current gain of the photocurrent is greater than 106. The electrical space constant of rat rods is greater than 25 μm, so that the electrical effects of the photocurrent are large enough at the rod synapses to permit single absorbed photons to be detected by the visual system. The photocurrent is apparently the primary sensory consequence of light absorption by rhodopsin. 相似文献
2.
A patch-clamp method was used for measuring light-induced currents (photocurrents) in single dark-adapted Peperomia metallica chloroplasts in a 'whole-thylakoid' configuration. The multi-phasic photocurrent profiles upon a train of multiple flashes (time separation between flashes in the train 1 s) show the following characteristics: (i) photocurrent generation originates from trans-thylakoid charge transfer accompanying reaction center (RC)- and Q-cycle turnover; (ii) a 15–30% decrease in the amplitude of the RC-driven current in the second and following flashes, concomitantly with an increase in the dark recovery time of the current; and (iii) a binary oscillation of the Q-cycle current generator with high activity in even numbered flashes. The decrease in amplitude and decay rate constant of the photocurrent in a double flash after dark adaptation are interpreted in terms of a change in the electric conductance of the thylakoid lumen. Data are interpreted to indicate a light control of the thylakoid lumen via a narrowing of the planar sheet-like structures by 1 to 3 single turnover flashes. A simple method is given to determine the bioenergetic and electric parameters of the thylakoid membrane of a single chloroplast from the current profiles in a double flash. The data indicate that 1 s after a saturating flash the fraction of closed inactive centers is less than 3%. 相似文献
3.
《Biophysical journal》2022,121(9):1765-1776
In the past decade, optogenetics has become a nearly ubiquitous tool in neuroscience because it enables researchers to manipulate neural activity with high temporal resolution and genetic specificity. Rational engineering of optogenetic tools has produced channelrhodopsins with a wide range of kinetics and photocurrent magnitude. Genome mining for previously unidentified species of rhodopsin has uncovered optogenetic tools with diverse spectral sensitivities. However, rational engineering of a rhodopsin has thus far been unable to re-engineer spectral sensitivity while preserving full photocurrent. Here, we developed and characterized ChroME-mTFP, a rhodopsin-fluorescent protein fusion that drives photocurrent through Förster resonance energy transfer (FRET). This FRET-opsin mechanism artificially broadened the activation spectrum of the blue-green-light-activated rhodopsin ChroME by approximately 50 nm, driving higher photocurrent at blue-shifted excitation wavelengths without sacrificing kinetics. The excitation spectra’s increase at short wavelengths enabled us to optogenetically excite neurons at lower excitation powers with shorter wavelengths of light. Increasing this rhodopsin’s sensitivity to shorter, bluer wavelengths pushes it toward dual-channel, crosstalk-free optogenetic stimulation and imaging with green-light-activated sensors. However, this iteration of FRET-opsin suffers from some imaging-light-induced photocurrent crosstalk from green or yellow light due to maintained, low-efficiency excitation at longer wavelengths. 相似文献
4.
Changes in cGMP concentration correlate with some, but not all, aspects of the light-regulated conductance of frog rod photoreceptors 总被引:2,自引:0,他引:2
R H Cote G D Nicol S A Burke M D Bownds 《The Journal of biological chemistry》1986,261(28):12965-12975
Cyclic GMP has been implicated in controlling the light-regulated conductance of rod photoreceptors of the vertebrate retina. However, there is little direct evidence correlating changes in cGMP concentration with the light-regulated permeability mechanism in living cells. A preparation of intact frog rod outer segments suspended in a Ringer's medium containing low Ca2+ has been used to demonstrate that initial changes in total cellular cGMP concentration parallel changes in the light-regulated membrane current over a wide range of light intensities. At light intensities bleaching from 160 to 5.6 X 10(6) rhodopsin molecules/rod/s, decreases in the response latency for the cGMP kinetics parallel decreases in the latent period of the electrical response. Further, changes in the rate of the cGMP decrease parallel the rate of membrane current suppression as the light intensity is varied. Up to 10(5) cGMP molecules are hydrolyzed per photolyzed rhodopsin, consistent with in vitro studies showing that each bleached rhodopsin can activate over 100 phosphodiesterase molecules. Addition of the Ca2+ ionophore, A23187, does not affect the initial kinetics of the cGMP decrease or of the electrical response, excluding a direct role for Ca2+ in the initial events of phototransduction. These results are consistent with cGMP being the intracellular messenger that links rhodopsin isomerization with changes in membrane permeability upon illumination. It is unlikely, however, that light-induced changes in total cGMP concentration are the sole regulators of membrane current. This is suggested by several observations: at bright light intensities, the subsecond light-induced cGMP decrease is essentially complete prior to complete suppression of membrane current; maximal light-induced decreases in cGMP concentration occur at all light intensities tested, whereas the extent of membrane current suppression varies over the same range of light intensities; changing the external Ca2+ concentration from 1 mM to 10 nM in the dark causes an increase in membrane current that is significantly more rapid than corresponding changes in cGMP concentration. Thus, light-induced changes in total cellular cGMP concentration correlate with some, but not all, aspects of the visual excitation process in vertebrate photoreceptors. 相似文献
5.
Photoreceptor currents of the multicellular green alga Volvox carteri were analyzed using a dissolver mutant. The photocurrents are restricted to the eyespot region of somatic cells. Photocurrents are detectable from intact cells and excised eyes. The rhodopsin action spectrum suggests that the currents are induced by Volvox rhodopsin. Flash-induced photocurrents are a composition of a fast Ca2+-carried current (PF) and a slower current (PS), which is carried by H+. PF is a high-intensity response that appears with a delay of less than 50 micros after flash. The stimulus-response curve of its initial rise is fit by a single exponential and parallels the rhodopsin bleaching. These two observations suggest that the responsible channel is closely connected to the rhodopsin, both forming a tight complex. At low flash energies PS is dominating. The current delay increases up to 10 ms, and the PS amplitude saturates when only a few percent of the rhodopsin is bleached. The data are in favor of a second signaling system, which includes a signal transducer mediating between rhodopsin and the channel. We present a model of how different modes of signal transduction are accomplished in this alga under different light conditions. 相似文献
6.
Kinetics of the Photocurrent of Retinal Rods 总被引:19,自引:1,他引:18
The shapes of the photocurrent responses of rat rods, recorded with microelectrodes from the receptor layer of small pieces of isolated retinas, have been investigated as a function of temperature and of stimulus energy. Between 27 and 37°C the responses to short flashes can be described formally as the output of a chain of at least four linear low-pass filters with time constants in the range 50-100 msec. The output of the filter chain is then distorted by a nonlinear amplitude-limiting process with a hyperbolic saturation characteristic. Flashes producing ~30 photons absorbed per rod yield responses of half-maximal size independently of temperature. The maximum response amplitude is that just sufficient to cancel the dark current. The rate of rise of a response is proportional to flash energy up to the level of 105 photons absorbed per rod, where hyperbolic rate saturation ensues. The responses continue to increase in duration with even more intense flashes until, at the level of 107 photons absorbed per rod, they last longer than 50 min. The time-courses of the photocurrent and of the excitatory disturbance in the rod system are very similar. The stimulus intensity at which amplitude saturation of the photocurrent responses begins is near that where psychophysical “rod saturation” is seen. An analysis of these properties leads to the following conclusions about the mechanism of rod excitation. (a) The kinetics of the photocurrent bear no simple relation to the formation or decay of any of the spectroscopic intermediates so far detected during the photolysis of rhodopsin. (b) The forms of both the amplitude- and rate-limiting processes are not compatible with organization of rhodopsin into “photoreceptive units” containing more than 300 chromophores. Even at high stimulus intensities most rhodopsin chromophores remain connected to the excitatory apparatus of rods. (c) The maximum rate of rise of the photocurrent is too fast to be consistent with the infolded disks of a rod outer segment being attached to the overlying plasma membrane. Most of the disks behave electrically as if isolated within the cell. (d) Control of the photocurrent at the outer segment membrane is not achieved by segregation of the charge carriers of the current within the rod disks. Instead, it is likely to depend on control of the plasma membrane permeability by an agent released from the disks. 相似文献
7.
E Nasi 《The Journal of general physiology》1991,97(1):55-72
Light-dependent membrane currents were recorded from solitary Lima photoreceptors with the whole-cell clamp technique. Light stimulation from a holding voltage near the cell's resting potential evokes a transient inward current graded with light intensity, accompanied by an increase in membrane conductance. While the photocurrent elicited by dim flashes decays smoothly, at higher stimulus intensities two kinetically distinct components become visible. Superfusion with TEA or intracellular perfusion with Cs do not eliminate this phenomenon, indicating that it is not due to the activation of the Ca-sensitive K channels that are present in these cells. The relative amplitude of the late component vs. the early peak of the light response is significantly more pronounced at -60 mV than at -40 mV. At low light intensities the reversal potential of the photocurrent is around 0 mV, but with brighter lights no single reversal potential is found; rather, a biphasic response with an inward and an outward component can be seen within a certain range of membrane voltages. Light adaptation through repetitive stimulation with bright flashes diminishes the amplitude of the early but not the late phase of the photocurrent. These observations can be accounted for by postulating two separate light-dependent conductances with different ionic selectivity, kinetics, and light sensitivity. The light response is also shown to interact with some of the voltage-sensitive conductances: activation of the Ca current by a brief conditioning prepulse is capable of attenuating the photocurrent evoked by a subsequent test flash. Thus, Ca channels in these cells may not only shape the photoresponse, but also participate in the process of light adaptation. 相似文献
8.
Characteristics of Drosophila rhodopsin in wild-type and norpA vision transduction mutants 总被引:3,自引:3,他引:0
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S E Ostroy 《The Journal of general physiology》1978,72(5):717-732
The properties of the major visual pigment of Drosophila melanogaster were evaluated. The visual pigment was isolated from other protein components using acrylamide gel electrophoresis and spectral identification. Sodium dodecyl sulfate (SDS) acrylamide gels of the isolated visual pigment gave a single protein subunit with a mol wt of 37,000 daltons. The rhodopsin480 molar extinction coefficient was 35,000 liter/mol-cm (+/- 2,700 SE). The metarhodopsin580 molar extinction coefficient was approximately 56,000 liter/mol-cm. Microspectrophotometry was used to compare the rhodopsin concentrations in wild-type flies and norpA vision transduction mutants. At 2 days of age (12 h dark-12 h light cycle, 19 degrees C) all of the norpA flies exhibited a similar rhodopsin concentration (75% of the wild-type strain). By 21 days of age some of the norpA alleles showed substantially reduced rhodopsin concentrations (16-43% of normal), whereas others showed no major age-dependent decreases (68-77%). Temperature and light-dark cycle affected the reduction. Alleles with no receptor potential exhibited the largest decreases in rhodopsin concentration. The data indicate that the norpA phototransduction mutant has a defect in the system responsible for maintaining the rhodopsin480 concentration. This defect in the rhodopsin maintenance system does not appear to be the cause of the reduced electroretinogram (ERG) amplitude observed in some of these mutants, but instead is a consequence of the decrease in ERG amplitude, or the flaw(s) responsible for the decrease in ERG amplitude. 相似文献
9.
"Either-or" two-slit interference: stable coherent propagation of individual photons through separate slits
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Alkon DL 《Biophysical journal》2001,80(5):2056-2061
In quantum theory, nothing that is observable, be it physical, chemical, or biological, is separable from the observer. Furthermore, ". all possible knowledge concerning that object is given by its wave function" (Wigner, E. 1967. Symmetries and Reflections. Indiana University Press, Bloomington, IN), which can only describe probabilities of future events. In physical systems, quantum mechanical probabilistic events that are microscopic must, in turn, account for macroscopic events that are associated with a greater degree of certainty. In biological systems, probabilistic statistical mechanical events, such as secretion of microscopic synaptic vesicles, must account for macroscopic postsynaptic potentials; probabilistic single-channel events sum to produce a macroscopic ionic current across a cell membrane; and bleaching of rhodopsin molecules (responsible for quantal potential "bumps") produces a photoreceptor generator potential. Among physical systems, a paradigmatic example of how quantum theory applies to the observation of events concerns the interactions of particles (e.g., photons, electrons) with the two-slit apparatus to generate an interference pattern from a single common light source. For two-slit systems that use two independent laser sources with brief (<1 ms) intervals of mutual coherence (Paul, H. 1986. Rev. Modern Phys. 58:209-231), each photon has been considered to arise from both beams and has a probability amplitude to pass through each of the two slits. Here, a single laser source two-slit interference system was constructed so that each photon has a probability amplitude to pass through only one or the other, but not both slits. Furthermore, all photons passing through one slit could be distinguished from all photons passing through the other slit before their passage. This "either-or" system produced a stable interference pattern indistinguishable from the interference produced when both slits were accessible to each photon. Because this system excludes the interaction of one photon with both slits, phase correlation of photon movements derives from the "entanglement" of all photon wave functions due to their dependence on a common laser source. Because a laser source (as well as Young's original point source) will have stable time-averaged spatial coherence even at low intensities, the "either-or" two-slit interference can result from distinct individual photons passing one at a time through one or the other slit-rather than wave-like behavior of individual photons. In this manner, single, successive photons passing through separate slits will assemble over time in phase-correlated wave distributions that converge in regions of low and high probability. 相似文献
10.
Effect of pH buffer molecules on the light-induced currents from oriented purple membrane 总被引:3,自引:3,他引:0
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The effect of pH buffers on the microsecond photocurrent component, B2, of oriented purple membranes has been studied. We found that under low salt conditions (less than 10 mM monovalent cationic salt) pH buffers can dramatically alter the waveform of the B2 component. The effect is induced by the protonation process of the buffer molecules by protons expelled from the membrane. These effects can be classified according to the charge transition upon protonation of the buffer. Buffers that carry two positive charges in their protonated form add a negative current component (N component) to B2. Almost all of the other buffers add a positive current component (P component) to B2, which is essentially a mirror image of the N component. Buffers with a pK less than 5.5 have only a small positive buffer component. The pH dependence of the buffer effect is closely related to the pK of the buffer; it requires that the buffer be in its unprotonated form. The rise time of the buffer component increases with the concentration of the buffer molecules. All the buffer effects can be inhibited by the addition of 5 mM of a divalent cation such as Ca2+. Reducing the surface potential slows down the N component but accelerates the P component without affecting the amplitude of the buffer effect significantly. Many of the buffer effects can be explained if we assume that upon protonation of the buffer by a proton expelled from the membrane by light, the buffer molecules move toward the membrane. This backward movement of buffer molecules forms a counter current very similar to that due to cations discussed in Liu, S. Y., R. Govindjee, and T. G. Ebrey. (1990. Biophys. J. 57:951-963). 相似文献
11.
The early receptor current (ERC) is the charge redistribution occurring in plasma membrane rhodopsin during light activation of photoreceptors. Both the molecular mechanism of the ERC and its relationship to rhodopsin conformational activation are unknown. To investigate whether the ERC could be a time-resolved assay of rhodopsin structure-function relationships, the distinct sensitivity of modern electrophysiological tools was employed to test for flash-activated ERC signals in cells stably expressing normal human rod opsin after regeneration with 11-cis-retinal. ERCs are similar in waveform and kinetics to those found in photoreceptors. The action spectrum of the major R(2) charge motion is consistent with a rhodopsin photopigment. The R(1) phase is not kinetically resolvable and the R(2) phase, which overlaps metarhodopsin-II formation, has a rapid risetime and complex multiexponential decay. These experiments demonstrate, for the first time, kinetically resolved electrical state transitions during activation of expressed visual pigment in a unicellular environment (single or fused giant cells) containing only 6 x 10(6)-8 x 10(7) molecules of rhodopsin. This method improves measurement sensitivity 7 to 8 orders of magnitude compared to other time-resolved techniques applied to rhodopsin to study the role particular amino acids play in conformational activation and the forces that govern those transitions. 相似文献
12.
Rhodopsin phosphorylation inhibited by adenosine in frog rods: lack of effects on excitation 总被引:2,自引:0,他引:2
K Donner S Hemil? 《Comparative biochemistry and physiology. A, Comparative physiology》1985,81(2):431-439
The rod photocurrent was studied by recording the transretinal voltage from the aspartate-treated isolated frog retina before and after perfusion with 2 mM adenosine, which inhibited 60-80% of the light-induced rhodopsin phosphorylation. Adenosine did not affect the time courses of the flash photoresponses or the OFF responses after a steady light. The introduction of adenosine while the retina was illuminated by a steady background did not enhance the effect of light. Instead, the opposite change, due to PDE inhibition, was observed. The results indicate that rhodopsin phosphorylation does not determine the time course of the decay of excitation. 相似文献
13.
Transient elementary currents, bumps, stimulated by short dim light flashes were measured in ventral nerve photoreceptors of Limulus. It is demonstrated that light activates two types of bumps, which form two distinct components of the receptor current at higher light intensities. The two bump types, which are both assumed to be activated by single absorbed photons, differ in current amplitude and kinetic parameters. The current amplitude of one bump type is smaller than 0.3 nA and that of the other type is in the usual current range of up to several nanoamperes. The average latency of small bumps measured from the short stimulus flash is shorter than that of the large bumps. The small bumps have slower activation kinetics than the large bumps. It is demonstrated that with increasing flash intensity the small bumps overlap first and form a macroscopic current, on top of which the large bumps are superimposed. Results indicate that a single absorbed photon selectively activates only one kind of the enzyme cascades evoking one bump type. We conclude that the active meta conformation of a rhodopsin molecule selectively binds a specific type of G-protein, which is involved in the stimulation of one of the transduction cascades. The two bump types, which are the elements of two macroscopic current components support the previous assumption that light activates different transduction mechanisms in Limulus photoreceptors. 相似文献
14.
Transgenic mice bearing null or functional mutations are being used to define the roles of specific elements in phototransduction and also to time the molecular interactions. Genetic manipulation of the collision frequency between rhodopsin and transducin molecules identified this parameter as rate-limiting for the photoresponse onset. Genetic interference with rhodopsin phosphorylation and arrestin binding, transducin shut-off and calcium feedback has revealed their respective roles in shaping the response waveform. The timetable for all of these molecular events determines the amplitude, kinetics and reproducibility of the photoresponse. 相似文献
15.
Light-induced voltage noise in the photoreceptor of Drosophila melanogaster 总被引:4,自引:4,他引:0
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The Drosophila photoreceptor potential is thought to be composed of discrete unit potentials called bumps. The steady-state receptor potential and the accompanying voltage fluctuations were recorded intracellularly under steady illumination. The occurrence rate, effective amplitude, and duration of the bumps were deduced by assuming a shot noise model. Over a wide range of light intensity, the duration of bumps remained essentially constant (25-30 ms). Below the saturation intensity for the receptor potential, the bump rate was roughly proportional to the intensity, and the adjustment of bumps to smaller size at higher intensity was mainly responsible for the nonlinear behavior of the receptor potential. The reduction in size of bumps at increasing light intensity was found to be due mainly to the diminishing magnitude of the bump current, and not to some other secondary effects. The bump rate saturated at about 3 x 105-106 events/s. 相似文献
16.
Biochemical correlates of adaptation processes in isolated frog photoreceptor membranes 总被引:9,自引:9,他引:0
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《The Journal of general physiology》1976,68(1):1-11
Frog rod outer segments isolated in suspension can maintain much of their in vivo activity. This observation provides us with a simpler system than the intact retina for correlating biochemical and physiological changes. The relevant physiological process, a decrease of sodium permeability by illumination, is assayed as light suppression of outer segment swelling in a modified Ringer's solution. We report here that this decrease is observed over approximately 4 log units of input light intensity and varies with the logarithm of intensity at light levels which bleach between 5.102 and 5.104 rhodopsin molecules/outer segment-second. In this illumination range responsiveness to light decreases as intensity increases. This sensitivity control system may be linked to light-activated rhodopsin phosphorylation, for inhibitors of this reaction increase light sensitivity. The presence of a second system, which controls the maximum amplitude of in vitro response to light, is revealed in experiments with cyclic nucleotide phosphodiesterase inhibitors. Papaverine addition raises intracellular cyclic GMP (guanosine monophosphate) levels and increases the magnitude of the dark permeability, but does not have a large influence on the amount of illumination required for suppression of this permeability. The data suggest that sensitivity and amplitude, as they are expressed in this in vitro system, are regulated by pharmacologically distinct pathways which use two different light-sensitive enzyme systems. 相似文献
17.
Light-induced binding of 48-kDa protein to photoreceptor membranes is highly enhanced by phosphorylation of rhodopsin 总被引:13,自引:0,他引:13
The 48-kDa protein, a major protein of rod photoreceptor cells, is soluble in the dark but associates with the disk membranes when some (5-10%) of their rhodopsin has absorbed light and if this rhodopsin is additionally phosphorylated by ATP and rhodopsin kinase. If rhodopsin has been phosphorylated and regenerated prior to the protein binding experiment, the binding of 48-kDa protein depends on light but no longer on the presence of ATP. Another photoreceptor protein, GTP-binding protein, associates with both phosphorylated and unphosphorylated rhodopsin upon illumination. Excess GTP-binding protein thereby displaces 48-kDa protein from phosphorylated disks; this indicates competition between these two proteins for binding sites on illuminated phosphorylated rhodopsin molecules. 相似文献
18.
Istvan Szundi Roberto Bogomolni David S. Kliger 《The Journal of biological chemistry》2015,290(27):16585-16594
Channelrhodopsins, such as the algal phototaxis receptor Platymonas subcordiformis channelrhodopsin-2 (PsChR2), are light-gated cation channels used as optogenetic tools for photocontrol of membrane potential in living cells. Channelrhodopsin (ChR)-mediated photocurrent responses are complex and poorly understood, exhibiting alterations in peak current amplitude, extents and kinetics of inactivation, and kinetics of the recovery of the prestimulus dark current that are sensitive to duration and frequency of photostimuli. From the analysis of time-resolved optical absorption data, presented in the accompanying article, we derived a two-cycle model that describes the photocycles of PsChR2. Here, we applied the model to evaluate the transient currents produced by PsChR2 expressed in HEK293 cells under both fast laser excitation and step-like continuous illumination. Interpretation of the photocurrents in terms of the photocycle kinetics indicates that the O states in both cycles are responsible for the channel current and fit the current transients under the different illumination regimes. The peak and plateau currents in response to a single light step, a train of light pulses, and a light step superimposed on a continuous light background observed for ChR2 proteins are explained in terms of contributions from the two parallel photocycles. The analysis shows that the peak current desensitization and recovery phenomena are inherent properties of the photocycles. The light dependence of desensitization is reproduced and explained by the time evolution of the concentration transients in response to step-like illumination. Our data show that photocycle kinetic parameters are sufficient to explain the complex dependence of photocurrent responses to photostimuli. 相似文献
19.
Light reduces the excitation efficiency in the nss mutant of the sheep blowfly Lucilia 总被引:2,自引:2,他引:0
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S Barash E Suss D G Stavenga C T Rubinstein Z Selinger B Minke 《The Journal of general physiology》1988,92(3):307-330
The nss (no steady state) phototransduction mutant of the sheep blowfly Lucilia was studied electrophysiologically using intracellular recordings. The effects of the nss mutation on the receptor potential are manifested in the following features of the light response. (a) The responses to a flash or to dim lights are close to normal, but the receptor potential decays close to the baseline level during prolonged illumination after a critical level of light intensity is reached. (b) The decline of the response is accompanied by a large reduction in responsiveness to light that recovers within 20 s in the dark. (c) The full reduction in responsiveness to light is reached when approximately 13% of the photopigment molecules are converted from rhodopsin (R) to metarhodopsin (M). (d) A maximal net pigment conversion from R to M by blue light induces persistent inactivation in the dark, without an apparent voltage response. This inactivation could be abolished at any time by M-to-R conversion with orange light. The above features of the mutant indicate that the effect of the nss mutation on the light response of Lucilia is very similar to the effects of the transient receptor potential (trp) mutation on the photoreceptor potential of Drosophila. Noise analysis and voltage measurements indicate that the decay of the receptor potential is due to a severe reduction in the rate of occurrence of the elementary voltage responses (bumps). The bumps are only slightly modified in shape and amplitude during the decline of the response to light of medium intensity. There is also a large increase in response latency during intense background illumination. These results are consistent with the hypothesis that separate, independent mechanisms determine bump triggering and bump shape and amplitude. The nss mutation affects the triggering mechanism of the bump. 相似文献
20.
Light-induced photoreceptor apoptosis occurs in many forms of inherited retinal degeneration resulting in blindness in both vertebrates and invertebrates. Though mutations in several photoreceptor signaling proteins have been implicated in triggering this process, the molecular events relating light activation of rhodopsin to photoreceptor death are yet unclear. Here, we uncover a pathway by which activation of rhodopsin in Drosophila mediates apoptosis through a G protein-independent mechanism. This process involves the formation of membrane complexes of phosphorylated, activated rhodopsin and its inhibitory protein arrestin, and subsequent clathrin-dependent endocytosis of these complexes into a cytoplasmic compartment. Together, these data define the proapoptotic molecules in Drosophila photoreceptors and indicate a novel signaling pathway for light-activated rhodopsin molecules in control of photoreceptor viability. 相似文献