Light adaptation and dark adaptation of human rod photoreceptors measured from the <i>a</i>‐wave of the electroretinogram

Thomas, Meredith; Lamb, Trevor D

doi:10.1111/j.1469-7793.1999.0479p.x

Cited by 113 publications

(110 citation statements)

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“…Similar abilities to remember a once-presented stimulus on the level of an individual receptor, and to quickly respond at the system level, have been observed for visual and olfactory systems, both mediated by G protein-coupled receptors (19,20). For example, light adaptation occurs within several seconds and begins at intensities so low that most photoreceptors receive only a few photons (20).…”

Section: Discussionmentioning

confidence: 92%

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Memory in receptor–ligand-mediated cell adhesion

Zarnitsyna¹,

Huang²,

Zhang³

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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Single-molecule biomechanical measurements, such as the force to unfold a protein domain or the lifetime of a receptor-ligand bond, are inherently stochastic, thereby requiring a large number of data for statistical analysis. Sequentially repeated tests are generally used to obtain a data ensemble, implicitly assuming that the test sequence consists of independent and identically distributed (i.i.d.) random variables, i.e., a Bernoulli sequence. We tested this assumption by using data from the micropipette adhesion frequency assay that generates sequences of two random outcomes: adhesion and no adhesion. Analysis of distributions of consecutive adhesion events revealed violation of the i.i.d. assumption, depending on the receptor-ligand systems studied. These include Markov sequences with positive (T cell receptor interacting with antigen peptide bound to a major histocompatibility complex) or negative (homotypic interaction between C-cadherins) feedbacks, where adhesion probability in the next test was increased or decreased, respectively, by adhesion in the immediate past test. These molecular interactions mediate cell adhesion and cell signaling. The ability to ''remember'' the previous adhesion event may represent a mechanism by which the cell regulates adhesion and signaling.adhesion frequency assay ͉ Markov sequence ͉ single-molecule mechanics ͉ Bernoulli sequence B iomechanical studies of protein, DNA, and RNA at the level of single molecules provide insights that complement information obtained from conventional measurements on ensembles of large numbers of molecules (1). These experiments employ ultrasensitive force techniques, for example, atomic force microscopy (2) and the biomembrane force probe technique (3), to mechanically characterize a single molecule that physically links the force sensor to a sample surface. Fig. 1 [and supporting information (SI) Movie 1] illustrate a simple experiment: the micropipette adhesion frequency assay (4). A human red blood cell (RBC) pressurized by micropipette aspiration is used as an adhesion sensor to test interactions between ligands coated on the RBC membrane and receptors expressed on a second cell (Fig. 1 A). The receptor-expressing cell is put into contact with the RBC for a given duration (Fig. 1B) and then retracted. If adhesion results, retraction will stretch the RBC (Fig. 1C), otherwise the RBC will smoothly return to its initial shape (Fig. 1D). When adhesion does occur, additional quantities can be measured by using the RBC picoforce transducer or any other ultrasensitive force technique, including rupture force (3), adhesion lifetime (2), molecular elasticity (5), protein unfolding (6), and protein refolding (7).Single-molecule biomechanical measurements are inherently stochastic because molecular events (e.g., unfolding of a protein domain or unbinding of a receptor-ligand bond) are determined not only by the weak, noncovalent interactions (within a single molecule or between two interacting molecules) but also by thermal excitations from the envi...

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Section: Discussionmentioning

confidence: 92%

“…For example, light adaptation occurs within several seconds and begins at intensities so low that most photoreceptors receive only a few photons (20). The duration of the adaptation is in turn determined by the lifetimes of the chemical processes underlying the adaptive response.…”

Section: Discussionmentioning

confidence: 99%

Memory in receptor–ligand-mediated cell adhesion

Zarnitsyna¹,

Huang²,

Zhang³

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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“…The methods used for recording the ERG, for presenting stimuli and for calculating bleaching levels were closely similar to those described by Smith & Lamb (1997) and Thomas & Lamb (1999). In brief, a conductive thread electrode (DTL, UniMed Electrode Supplies, Farnham, UK), placed loosely in the lower fornix of one eye, was used to record the ERG from three adult subjects (the authors) with normal vision apart from minor errors of refraction.…”

Section: Methodsmentioning

confidence: 99%

“…The right-hand panels show the same results as the left panels, but on a faster time scale and an enlarged vertical scale. Typically, each point was derived from four flash pairs, delivered at intervals of 60 s. However, for the measurements on backgrounds in C and D, the repetition interval was reduced to 45 or 30 s for flash separations shorter than 30 s. The curves plot the sum of assumed photopic and scotopic components, each representing the fading of an equivalent background light, as specified by the expressions in eqns (8) and (12) of Thomas & Lamb (1999); in addition, for experiments conducted in the presence of background illumination, we added the real light. For the photopic recovery, the time constant was 0.1 s for both subjects, and the amplitude of the component was 0.18 (TDL) and 0.19 (CF) of the total signal.…”

Section: Recovery From Probe Flash: Choice Of Stimulus Repetition Intmentioning

confidence: 99%

Time course of the flash response of dark‐ and light‐adapted human rod photoreceptors derived from the electroretinogram

Friedburg

Thomas

Lamb

2001

The Journal of Physiology

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Double-flash techniques have been used for decades to monitor the recovery of the a-wave and b-wave of the electroretinogram (ERG) following a first flash (e.g. Dodt, 1952;Mahneke, 1957;Burian & Spivey, 1959;Elenius, 1967Elenius, , 1969Gjötterberg, 1974). In the 1960s, it became clear that the a-wave of the ERG reflected photoreceptor activity (Brown & Wiesel, 1961), though it was not until the 1990s that quantitative analysis of the a-wave provided a faithful measure of photoreceptor currents (see, for example, Hood & Birch, 1990. Even so, the a-wave itself only provides information about photoreceptor currents at the very earliest times after a flash, before the b-wave and other post-receptoral signals intrude.With the insight provided by recent knowledge, several groups have monitored photoreceptor responses at later times, by recording the a-wave elicited by what has become known as a 'paired-flash' stimulus, in which an arbitrary test flash is followed at a range of time intervals by an intense probe flash (in human: Birch et al. 1995;Pepperberg et al. 1996Pepperberg et al. , 1997Cideciyan et al. 1998; in mouse: Lyubarsky & Pugh, 1996;Goto et al. 1996;Hetling & Pepperberg, 1999; reviewed in Pepperberg et al. 2000). In this technique, the amplitude of the response to the intense probe flash (i.e. the maximal response that can be elicited) provides a measure of the remaining circulating current in the photoreceptors at a particular time after the test flash. Although the method is tedious, in requiring numerous repetitions with different intervals between test and probe flashes, it currently provides the only means for extracting the response from photoreceptors in the living eye, at more than about 10 ms after a flash. 1. The a-wave of the electroretinogram was recorded from human subjects with normal vision, using a corneal electrode and ganzfeld stimulation. We applied the paired-flash technique, in which an intense 'probe' flash was delivered at different times after a 'test' flash. The amplitude of the probe-flash response provided a measure of the circulating current remaining at the appropriate time after the test flash.2. We extended previous methods by measuring not at a fixed time, but at a range of times after the probe flash, and then calculating the ratio of the 'test-plus-probe' response to the 'probealone' response, as a function of time.3. Under dark-adapted conditions the rod response derived by the paired-flash technique (in response to a relatively dim test flash) peaked at ca 120 ms, with a fractional sensitivity at the peak of ca 0.1 Td _1 s _1 .4. As reported previously, background illumination reduced the maximal response, reflecting a reduction in rod circulating current. In addition, it shortened the time to peak (to ca 70 ms at an intensity of 170 Td), and reduced the flash sensitivity measured at the peak. The flash sensitivity declined approximately according to Weber's Law, with a 10-fold reduction occurring at an intensity of 100-200 Td. We could not reliably measure responses ...

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“…4B) have been conducted in both human subjects and in mice, with test flashes that extend into the range of significant rhodopsin bleaching. 22,23,26,27,39 As noted above, the Fig. 4 experiments employed subtraction of a single response, one representing a cone contribution assumed constant under the investigated conditions, to isolate the rod-mediated component of the probe flash responses.…”

Section: Time Course Of Derived Responsementioning

confidence: 99%