The common backswimmer, Notonecta glauca, uses vision by day and night for functions such as underwater prey animal capture and flight in search of new habitats. Although previous studies have identified some of the physiological mechanisms facilitating such flexibility in the animal's vision, neither the biophysics of Notonecta photoreceptors nor possible cellular adaptations are known. Here, we studied Notonecta photoreceptors using patch-clamp and intracellular recording methods. Photoreceptor size (approximated by capacitance) was positively correlated with absolute sensitivity and acceptance angles. Information rate measurements indicated that large and more sensitive photoreceptors performed better than small ones. Our results suggest that backswimmers are adapted for vision in both dim and wellilluminated environments by having open-rhabdom eyes with large intrinsic variation in absolute sensitivity among photoreceptors, exceeding those found in purely diurnal or nocturnal species. Both electrophysiology and microscopic analysis of retinal structure suggest two retinal subsystems: the largest peripheral photoreceptors provide vision in dim light and the smaller peripheral and central photoreceptors function primarily in sunlight, with light-dependent pigment screening further contributing to adaptation in this system by dynamically recruiting photoreceptors with varying sensitivity into the operational pool.

BackgroundCelecoxib (Celebrex), a widely prescribed selective inhibitor of cyclooxygenase-2, can modulate ion channels independently of cyclooxygenase inhibition. Clinically relevant concentrations of celecoxib can affect ionic currents and alter functioning of neurons and myocytes. In particular, inhibition of Kv2.1 channels by celecoxib leads to arrhythmic beating of Drosophila heart and of rat heart cells in culture. However, the spectrum of ion channels involved in human cardiac excitability differs from that in animal models, including mammalian models, making it difficult to evaluate the relevance of these observations to humans. Our aim was to examine the effects of celecoxib on hERG and other human channels critically involved in regulating human cardiac rhythm, and to explore the mechanisms of any observed effect on the hERG channels.Methods and ResultsCelecoxib inhibited the hERG, SCN5A, KCNQ1 and KCNQ1/MinK channels expressed in HEK-293 cells with IC50s of 6.0 µM, 7.5 µM, 3.5 µM and 3.7 µM respectively, and the KCND3/KChiP2 channels expressed in CHO cells with an IC50 of 10.6 µM. Analysis of celecoxib's effects on hERG channels suggested gating modification as the mechanism of drug action.ConclusionsThe above channels play a significant role in drug-induced long QT syndrome (LQTS) and short QT syndrome (SQTS). Regulatory guidelines require that all new drugs under development be tested for effects on the hERG channel prior to first administration in humans. Our observations raise the question of celecoxib's potential to induce cardiac arrhythmias or other channel related adverse effects, and make a case for examining such possibilities.

Visual transduction in rhabdomeric photoreceptors is compartmentalized and discretized. Signals of individual microvilli, the quantum bumps, are electrotonically summed, producing a graded response. Intrinsic dispersion of quantum bump latencies is thought to introduce noise and degrade signal transfer. Here, we found profound differences in the information rate and signaling bandwidth between in vitro patch-clamp and in vivo intracellular recordings of Periplaneta americana photoreceptors and traced them to the properties of quantum bumps and membrane resistance. Comparison of macroscopic and elementary light responses revealed differences in quantum bump summation and membrane resistance in vivo versus in vitro. Modeling of voltage bumps suggested that current bumps in vivo should be much bigger and faster than those actually recorded in vitro. Importantly, the group-average latency of dark-adapted photoreceptors was 30 ± 8 ms in intracellular ( n = 34) versus 70 ± 19 ms in patch-clamp ( n = 57) recordings. Duration of composite responses increased with mean latency because bump dispersion depended on mean latency. In vivo, latency dispersion broadened the composite response by 25% on average and slowed its onset. However, in the majority of photoreceptors, the characteristic durations of multiphoton impulse responses to 1-ms stimuli did not exceed the durations of mean voltage bumps. Consistently, we found strong associations between the latency and onset kinetics of the macroscopic response, on the one hand and the higher-frequency signal gain and information rate of the photoreceptor, on the other hand, indicating a direct connection between quantum bump latency and its dispersion and the signaling bandwidth. NEW & NOTEWORTHY When stimulated by light, microvilli of rhabdomeric photoreceptors produce discrete signals characterized by variable latencies. We show that this intrinsic latency dispersion restricts signaling bandwidth and information rate of photoreceptors in Periplaneta americana. Profound differences are found between the properties of photoreceptor responses in vivo and in vitro.

Nocturnal vision in insects depends on the ability to reliably detect scarce photons. Nocturnal insects tend to have intrinsically more sensitive and larger rhabdomeres than diurnal species. However, large rhabdomeres have relatively high membrane capacitance (C m), which can strongly low-pass filter the voltage bumps, widening and attenuating them. To investigate the evolution of photoreceptor signaling under near dark, we recorded elementary current and voltage responses from a number of species in six insect orders. We found that the gain of phototransduction increased with C m , so that nocturnal species had relatively large and prolonged current bumps. Consequently, although the voltage bump amplitude correlated negatively with C m , the strength of the total voltage signal increased. Importantly, the background voltage noise decreased strongly with increasing C m , yielding a notable increase in signal-to-noise ratio for voltage bumps. A similar decrease in the background noise with increasing C m was found in intracellular recordings in vivo. Morphological measurements of rhabdomeres were consistent with our C m estimates. Our results indicate that the increased photoreceptor C m in nocturnal insects is a major sensitivity-boosting and noise-suppressing adaptation. However, by requiring a compensatory increase in the gain of phototransduction, this adaptation comes at the expense of the signaling bandwidth.

Visual signal transmission by Drosophila melanogaster photoreceptors is mediated by a Gq protein that activates a phospholipase C (PLC). Mutations and deficiencies in expression of either of these proteins cause severe defects in phototransduction.Here we investigated whether these proteins are also involved in the cockroach, Periplaneta americana, phototransduction by silencing Gq α-subunit (Gqα) and phosphoinositide-specific phospholipase C (PLC) by RNA interference and observing responses to single photons (quantum bumps, QB). We found (1) non-specific decreases in membrane resistance, membrane capacitance and absolute sensitivity in the photoreceptors of both Gqα and PLC knockdowns, and (2) small changes in QB statistics. Despite significant decreases in expressions of Gq and PLC mRNA, the changes in QB properties were surprisingly modest, with mean latencies increasing by ~ 10%, and without significant decrease in their amplitudes. To better understand our results, we used a mathematical model of the phototransduction cascade. By modifying the Gq and PLC abundances, and diffusion rates for Gq, we found that QB latencies and amplitudes deteriorated noticeably only after large decreases in the protein levels, especially when Gq diffusion was slow. Also, reduction in Gq but not PLC lowered quantum efficiency. These results suggest that expression of the proteins may be redundant.

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The information transfer rate provides an objective and rigorous way to quantify how much information is being transmitted through a communications channel whose input and output consist of time-varying signals. However, current estimators of information content in continuous signals are typically based on assumptions about the system's linearity and signal statistics, or they require prohibitive amounts of data. Here we present a novel information rate estimator without these limitations that is also optimized for computational efficiency. We validate the method with a simulated Gaussian information channel and demonstrate its performance with two example applications. Information transfer between the input and output signals of a nonlinear system is analyzed using a sensory receptor neuron as the model system. Then, a climate data set is analyzed to demonstrate that the method can be applied to a system based on two outputs generated by interrelated random processes. These analyses also demonstrate that the new method offers consistent performance in situations where classical methods fail. In addition to these examples, the method is applicable to a wide range of continuous time series commonly observed in the natural sciences, economics and engineering.

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