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1.
Opt Express ; 32(7): 12982-12991, 2024 Mar 25.
Article in English | MEDLINE | ID: mdl-38571104

ABSTRACT

Quantum dense metrology (QDM) performs high-precision measurements by a two-mode entangled state created by an optical parametric amplifier (PA), where one mode is a meter beam and the other is a reference beam. In practical applications, the photon losses of meter beam are unavoidable, resulting in a degradation of the sensitivity. Here, we employ coherent feedback that feeds the reference beam back into the PA by a beam splitter to enhance the sensitivity in a lossy environment. The results show that the sensitivity is enhanced significantly by adjusting the splitting ratio of the beam splitter. This method may find its potential applications in QDM. Furthermore, such a strategy that two non-commuting observables are simultaneous measurements could provide a new way to individually control the noise-induced random drift in phase or amplitude of the light field, which would be significant for stabilizing the system and long-term precision measurement.

2.
Opt Express ; 31(4): 6499-6513, 2023 Feb 13.
Article in English | MEDLINE | ID: mdl-36823904

ABSTRACT

We propose an alternative scheme for phase estimation in a Mach-Zehnder interferometer (MZI) with photon recycling. It is demonstrated that with the same coherent-state input and homodyne detection, our proposal possesses a phase sensitivity beyond the traditional MZI. For instance, it can achieve an enhancement factor of Ć¢ĀˆĀ¼9.32 in the phase sensitivity compared with the conventional scheme even with a photon loss of 10% on the photon-recycled arm. From another point of view, the quantum CramĆ©r-Rao bound (QCRB) is also investigated. It is found that our scheme is able to achieve a lower QCRB than the traditional one. Intriguingly, the QCRB of our scheme is dependent of the phase shift ƏĀ• while the traditional scheme has a constant QCRB regardless of the phase shift. Finally, we present the underlying mechanisms behind the enhanced phase sensitivity. We believe that our results provide another angle from which to enhance the phase sensitivity in a MZI via photon recycling.

3.
Phys Rev Lett ; 130(7): 073601, 2023 Feb 17.
Article in English | MEDLINE | ID: mdl-36867793

ABSTRACT

Interferometers are crucial for precision measurements, including gravitational waves, laser ranging, radar, and imaging. The phase sensitivity, the core parameter, can be quantum-enhanced to break the standard quantum limit (SQL) using quantum states. However, quantum states are highly fragile and quickly degrade with losses. We design and demonstrate a quantum interferometer utilizing a beam splitter with a variable splitting ratio to protect the quantum resource against environmental impacts. The optimal phase sensitivity can reach the quantum CramĆ©r-Rao bound of the system. This quantum interferometer can greatly reduce the quantum source requirements in quantum measurements. In theory, with a 66.6% loss rate, the sensitivity can break the SQL using only a 6.0Ā dB squeezed quantum resource with the current interferometer rather than a 24Ā dB squeezed quantum resource with a conventional squeezing-vacuum-injected Mach-Zehnder interferometer. In experiments, when using a 2.0Ā dB squeezed vacuum state, the sensitivity enhancement remains at Ć¢ĀˆĀ¼1.6 dB via optimizing the first splitting ratio when the loss rate changes from 0% to 90%, indicating that the quantum resource is excellently protected with the existence of losses in practical applications. This strategy could open a way to retain quantum advantages for quantum information processing and quantum precision measurement in lossy environments.

4.
Phys Rev Lett ; 131(15): 150804, 2023 Oct 13.
Article in English | MEDLINE | ID: mdl-37897768

ABSTRACT

A quantum memory with the performances of low noise, high efficiency, and high bandwidth is of crucial importance for developing practical quantum information technologies. However, the excess noises generated during the highly efficient processing of quantum information inevitably destroy quantum state. Here, we present a quantum memory with built-in excess-noise eraser by integrating a photon-correlated quantum interferometry in quantum memory, where the memory efficiency can be enhanced and the excess noises can be suppressed to the vacuum level via destructive interference. This quantum memory is demonstrated in a rubidium vapor cell with a 10-ns-long photonics signal. We observe Ć¢ĀˆĀ¼80% noise suppression, the write-in efficiency enhancement from 87% to 96.2% without and with interferometry, and the corresponding memory efficiency excluding the noises from 70% to 77%. The fidelity is 93.7% at the single-photon level, significantly exceeding the no-cloning limit. Such interferometry-integrated quantum memory, the first expansion of quantum interference techniques to quantum information processing, simultaneously enables low noise, high bandwidth, high efficiency, and easy operation.

5.
Opt Express ; 30(7): 11514-11523, 2022 Mar 28.
Article in English | MEDLINE | ID: mdl-35473094

ABSTRACT

The SU (1,1)-type atom-light hybrid interferometer (SALHI) is a kind of interferometer that is sensitive to both the optical phase and atomic phase. However, the loss has been an unavoidable problem in practical applications and greatly limits the use of interferometers. Visibility is an important parameter to evaluate the performance of interferometers. Here, we experimentally demonstrate the mitigating effect of the loss on visibility of the SALHI via asymmetric gain optimization, where the maximum threshold of loss to visibility close to 100% is increased. Furthermore, we theoretically find that the optimal condition for the largest visibility is the same as that for the enhancement of signal-to-noise ratio (SNR) to the best value with the existence of the losses using the intensity detection, indicating that visibility can act as an experimental operational criterion for SNR improvement in practical applications. Improvement of the interference visibility means achievement of SNR enhancement. Our results provide a significant foundation for practical application of the SALHI in radar and ranging measurements.

6.
Phys Rev Lett ; 128(3): 033601, 2022 Jan 21.
Article in English | MEDLINE | ID: mdl-35119880

ABSTRACT

We present experimental and theoretical results on a new interferometer topology that nests a SU(2) interferometer, e.g., a Mach-Zehnder or Michelson interferometer, inside a SU(1,1) interferometer, i.e., a Mach-Zehnder interferometer with parametric amplifiers in place of beam splitters. This SU(2)-in-SU(1,1) nested interferometer (SISNI) simultaneously achieves a high signal-to-noise ratio (SNR), sensitivity beyond the standard quantum limit (SQL) and tolerance to photon losses external to the interferometer, e.g., in detectors. We implement a SISNI using parametric amplification by four-wave mixing (FWM) in Rb vapor and a laser-fed Mach-Zehnder SU(2) interferometer. We observe path-length sensitivity with SNR 2.2Ā dB beyond the SQL at power levels (and thus SNR) 2 orders of magnitude beyond those of previous loss-tolerant interferometers. We find experimentally the optimal FWM gains and find agreement with a minimal quantum noise model for the FWM process. The results suggest ways to boost the in-practice sensitivity of high-power interferometers, e.g., gravitational wave interferometers, and may enable high-sensitivity, quantum-enhanced interferometry at wavelengths for which efficient detectors are not available.

7.
Opt Lett ; 42(19): 4024-4027, 2017 Oct 01.
Article in English | MEDLINE | ID: mdl-28957188

ABSTRACT

We demonstrate a new phase-matching geometry for four-wave mixing processes in hot Rb85 vapor, in which all four fields propagate in different directions but two of them are degenerate in frequency. When used as a parametric amplifier with an injected seed, two types of quantum mechanically correlated twin-beam states, either frequency degenerate or nondegenerate, can be generated. The quantum noise reduction in the intensity difference is almost 7Ā dB for the nondegenerate type and nearly 5Ā dB for the degenerate type. The spatial nondegeneracy of the four waves allows a variety of configurations of parametric processes, leading to flexible control for both phase insensitive and sensitive parametric amplification. The spatially nondegenerate but frequency degenerate four-wave mixing process will find wide applications in quantum metrology, quantum communication, and quantum information of continuous variables.

8.
Opt Lett ; 42(9): 1752-1755, 2017 May 01.
Article in English | MEDLINE | ID: mdl-28454152

ABSTRACT

In studying quantum correlation and quantum memory of continuous variables of light fields and atoms, a crucial step is the retrieval of the quantum fields by converting an atomic spin wave to light, and retrieval efficiency is a crucial parameter. In this Letter, we implement a double-pass Raman scheme in Rb87 by incorporating coherent feedback. We find that the transfer efficiency from an atomic spin wave, which is generated from a Raman process in a high gain regime, to light fields is enhanced by the double-pass scheme as compared to the commonly used single-pass scheme. An atomic spin wave as high as 88% is read out, limited only by decoherence of the atomic spin waves. Our analysis shows that the enhancement effect is because a double-pass scheme introduced the coherent feedback mechanism which selects the spatial mode of an atomic spin wave via the correlated optical field and enhances the coupling efficiency between the atom and light. The correlations between the write-in and readout signals generated in such a two-pass Raman process are also better than the single-pass case. We believe such a two-pass scheme with feedback mechanism should be useful for studying continuous variables in quantum systems.

9.
Opt Express ; 24(16): 17766-78, 2016 Aug 08.
Article in English | MEDLINE | ID: mdl-27505745

ABSTRACT

Collective atomic excitation can be realized by the Raman scattering. Such a photon-atom interface can form an SU(1,1)-typed atom-light hybrid interferometer, where the atomic Raman amplification processes take the place of the beam splitting elements in a traditional Mach-Zehnder interferometer. We numerically calculate the phase sensitivities and the signal-to-noise ratios (SNRs) of this interferometer with the method of homodyne detection and intensity detection, and give their differences of the optimal phase points to realize the best phase sensitivities and the maximal SNRs from these two detection methods. The difference of the effects of loss of light field and atomic decoherence on measure precision is analyzed.

10.
Opt Express ; 23(8): 10009-17, 2015 Apr 20.
Article in English | MEDLINE | ID: mdl-25969042

ABSTRACT

We demonstrate experimentally controlled storage and retrieval of the optical phase information in a higher-order interference scheme based on Raman process in (87)Rb atomic vapor cells. An interference pattern is observed in intensity correlation measurement between the write Stokes field and the delayed read Stokes field as the phase of the Raman write field is scanned. This result implies that the phase information of the Raman write field can be written into the atomic spin wave via Raman process in a high gain regime and subsequently read out via a spin-wave enhanced Raman process, thus achieving optical storage of phase information. This technique should find applications in optical phase image storage, holography and information processing.

11.
Neural Plast ; 2015: 927817, 2015.
Article in English | MEDLINE | ID: mdl-26078886

ABSTRACT

Cordycepin has been widely used in oriental countries to maintain health and improve physical performance. Compound nerve action potential (CNAP), which is critical in signal conduction in the peripheral nervous system, is necessary to regulate physical performance, including motor system physiological and pathological processes. Therefore, regulatory effects of cordycepin on CNAP conduction should be elucidated. In this study, the conduction ability of CNAP in isolated frog sciatic nerves was investigated. Results revealed that cordycepin significantly decreased CNAP amplitude and conductive velocity in a reversible and concentration-dependent manner. At 50 mg/L cordycepin, CNAP amplitude and conductive velocity decreased by 62.18 Ā± 8.06% and 57.34% Ā± 6.14% compared with the control amplitude and conductive velocity, respectively. However, the depressive action of cordycepin on amplitude and conductive velocity was not observed in Ca(2+)-free medium or in the presence of Ca(2+) channel blockers (CdCl2/LaCl3). Pretreatment with L-type Ca(2+) channel antagonist (nifedipine/deltiazem) also blocked cordycepin-induced responses; by contrast, T-type and P-type Ca(2+) channel antagonists (Ni(2+)) failed to block such responses. Therefore, cordycepin decreased the conduction ability of CNAP in isolated frog sciatic nerves via L-type Ca(2+) channel-dependent mechanism.


Subject(s)
Action Potentials/drug effects , Deoxyadenosines/pharmacology , Neural Conduction/drug effects , Sciatic Nerve/drug effects , Sciatic Nerve/physiology , Animals , Anura , Calcium Signaling/drug effects , In Vitro Techniques
12.
Opt Express ; 21(9): 10490-5, 2013 May 06.
Article in English | MEDLINE | ID: mdl-23669906

ABSTRACT

We experimentally demonstrate efficient Raman conversion to respective Stokes and anti-Stokes fields in both pulsed and continuous modes with a Rb-87 atomic vapor cell. The conversion efficiency is about 40-50% for the Stokes field and 20-30% for the anti-Stokes field, respectively. This efficient conversion process is realized with coherent feedback of both the Raman pump and the frequency-converted fields (Stokes or anti-Stokes). The experimental setup is simple and can be applied easily to produce light sources with larger frequency shifts using other Raman media with long coherence time. They may have potential applications in nonlinear optics, Raman spectroscopy and precision measurement.


Subject(s)
Lasers , Spectrum Analysis, Raman/instrumentation , Computer-Aided Design , Equipment Design , Equipment Failure Analysis
13.
Phys Rev Lett ; 105(13): 133603, 2010 Sep 24.
Article in English | MEDLINE | ID: mdl-21230776

ABSTRACT

Coherent conversion between a Raman pump field and its Stokes field is observed in a Raman process with a strong atomic spin wave initially prepared by another Raman process operated in the stimulated emission regime. The oscillatory behavior resembles the Rabi oscillation in atomic population in a two-level atomic system driven by a strong light field. The Rabi-like oscillation frequency is found to be related to the strength of the prebuilt atomic spin wave. High conversion efficiency of 40% from the Raman pump field to the Stokes field is recorded and it is independent of the input Raman pump field. This process can act as a photon frequency multiplexer and may find wide applications in quantum information science.

14.
Nat Commun ; 10(1): 148, 2019 01 11.
Article in English | MEDLINE | ID: mdl-30635582

ABSTRACT

Quantum memories are essential for quantum information processing. Techniques have been developed for quantum memory based on atomic ensembles. The atomic memories through optical resonance usually suffer from the narrow-band limitation. The far off-resonant Raman process is a promising candidate for atomic memories due to broad bandwidths and high speeds. However, to date, the low memory efficiency remains an unsolved bottleneck. Here, we demonstrate a high-performance atomic Raman memory in 87Rb vapour with the development of an optimal control technique. A memory efficiency of above 82.0% for 6 ns~20 ns optical pulses is achieved. In particular, an unconditional fidelity of up to 98.0%, significantly exceeding the no-cloning limit, is obtained with the tomography reconstruction for a single-photon level coherent input. Our work marks an important advance of atomic memory towards practical applications in quantum information processing.

15.
Neurosci Lett ; 412(2): 108-13, 2007 Jan 29.
Article in English | MEDLINE | ID: mdl-17174470

ABSTRACT

Bis(7)-tacrine [bis(7)-tetrahydroaminacrine] acts as an AChE inhibitor and also exerts modulatory effects on many ligand-gated ion channels and voltage-gated Ca(2+) and K(+) channels. It has been reported previously that tacrine and some other AChE inhibitors suppressed I(K(A)) in central and peripheral neurons. The present study aimed to explore whether bis(7)-tacrine could modulate the function of native delayed rectifier potassium channels in DRG neurons and K(V)1.2 encoded potassium channels expressed in oocytes. We found that both delayed rectifier potassium currents (I(K(DR))) in rat DRG neurons and the currents recorded from oocytes expressing K(V)1.2 (I(K(K(V)1.2))) were suppressed by bis(7)-tacrine, the potency of which was two orders greater than that of tacrine. The IC(50) values for bis(7)-tacrine and tacrine inhibition of I(K(KD)) in DRG neurons were 0.72+/-0.05 and 58.3+/-3.7 microM, respectively; while the two agents inhibited I(K(K(V)1.2)) in oocytes with an IC(50) of 0.24+/-0.06 and 102.1+/-21.5 microM, respectively. The possible mechanism for bis(7)-tacrine inhibition of I(K(A)) and I(K(K(V)1.2)) was identified as the suppression of their activation, inactivation.


Subject(s)
Delayed Rectifier Potassium Channels/metabolism , Kv1.2 Potassium Channel/metabolism , Neurons, Afferent/metabolism , Potassium Channel Blockers/pharmacology , Tacrine/analogs & derivatives , Animals , Cells, Cultured , Cholinesterase Inhibitors/pharmacology , Delayed Rectifier Potassium Channels/drug effects , Dose-Response Relationship, Drug , Female , Ganglia, Spinal/cytology , Gene Transfer Techniques , Ion Channel Gating/drug effects , Ion Channel Gating/physiology , Kv1.2 Potassium Channel/drug effects , Kv1.2 Potassium Channel/genetics , Membrane Potentials/drug effects , Membrane Potentials/physiology , Neural Inhibition/drug effects , Neural Inhibition/physiology , Neurons, Afferent/drug effects , Oocytes/drug effects , Oocytes/metabolism , Patch-Clamp Techniques , Rats , Rats, Sprague-Dawley , Tacrine/pharmacology , Xenopus
16.
Eur J Pharmacol ; 796: 1-6, 2017 Feb 05.
Article in English | MEDLINE | ID: mdl-27988284

ABSTRACT

Cordycepin has important neuroprotective effects in hypoxic or ischemic insult. However, the direct electrophysiological evidence of cordycepin's neuroprotection from hypoxic or ischemic insult remains unknown. Hence, in this study, the electrophysiological mechanism by which cordycepin protects against ischemic and hypoxic damages has been studied using an energy-deprivation injury model through whole-cell patch clamp techniques. Results revealed that cordycepin (80ĀµM) significantly delayed hypoxia-induced membrane depolarization, including cordycepin reduced slope, and extended the duration of slow depolarization, prolonged the ability to generate spontaneous action potential (AP) firing, delayed the onset of rapid depolarization, and maintained the more hyperpolarized membrane potential after rapid depolarization. Additionally, cordycepin also delayed the hypoxia-induced decrease in the evoked AP amplitude. Furthermore, cordycepin can rescue the neuronal electrophysiological function after the 5min hypoxia pretreatment insult as seen the recovery on the evoked spike amplitude, membrane potential, and evoked AP latency during reoxygenation of hippocampal slices with cordycepin. Collectively, the results in this study provide direct evidence demonstrating the important neuroprotective effects of cordycepin against the hypoxic insult via improvement of the neuronal electrophysiological function, and the mechanism underlying the anti hypoxia-induced membrane depolarization is strongly recommended.


Subject(s)
CA1 Region, Hippocampal/cytology , Deoxyadenosines/pharmacology , Membrane Potentials/drug effects , Pyramidal Cells/cytology , Pyramidal Cells/drug effects , Action Potentials/drug effects , Animals , Cell Hypoxia/drug effects , Dose-Response Relationship, Drug , Evoked Potentials/drug effects , Rats , Rats, Sprague-Dawley , Time Factors
17.
Sheng Li Xue Bao ; 58(5): 494-9, 2006 Oct 25.
Article in Zh | MEDLINE | ID: mdl-17041736

ABSTRACT

To investigate the role of ion channels in the coupling responses of neutrophils to extracellular stimulus, it is necessary to study the membrane ion channel activities using patch-clamp technique. However, little has been known about the ion channel activities in neutrophils due to the difficulties in forming giga-seal with pipettes because of small diameter of neutrophils and the easily developed polarization. Some studies indicated that favorable results could be achieved through pretreatment at low temperature before electrophysiological recordings. But it remains unclear whether the pretreatment affects the membrane current and why the seal rate increases after low temperature pretreatment. The purpose of this study was to investigate the effects of 4 degrees C pretreatment on the membrane current and cell polarity in human neutrophils. In the experiments, human neutrophils were isolated from fresh peripheral blood of healthy volunteers and divided into two groups (room temperature group and 4 degrees C pretreatment group). Voltage-dependent K(+) (Kv) currents were recorded in whole-cell voltage-clamp mode and large-conductance Ca(2+)-activated K(+) (BK(Ca)) currents were recorded using inside-out patches. The results showed that 4 degrees C pretreatment significantly inhibited cell polarity (P<0.05), and it took more time for neutrophils to form a polarity-cycle [(534+/-32) s, n=20] compared with those at room temperature [(257+/-24) s, n=20]. Meanwhile, seal rate significantly increased in 4 degrees C pretreatment group (64%) compared with that in the room temperature group (27.5%). The seal rate and cell polarity rate during 0 approximately 1 min after 4 degrees C pretreatment were significantly different from those at room temperature, while no significant difference was found during 9 approximately 10 min between the two groups. Our results suggest that 4 degrees C pretreatment can inhibit cell polarity and increase seal rate, but has no effects on membrane currents. It is also suggested that 0 approximately 1 min after 4 degrees C pretreatment is a more suitable time for electrophysiological recording in neutrophils.


Subject(s)
Neutrophils/physiology , Cell Polarity , Cold Temperature , Humans , Large-Conductance Calcium-Activated Potassium Channels/physiology , Membrane Potentials , Potassium Channels, Voltage-Gated/physiology
18.
PLoS One ; 9(6): e98894, 2014.
Article in English | MEDLINE | ID: mdl-24896240

ABSTRACT

Gastric cancer (GC) is one of the leading causes of cancer death in the world. The role of histone deacetylase 4 (HDAC4) in specific cell and tissue types has been identified. However, its biological roles in the development of gastric cancer remain largely unexplored. Quantitative real time PCR (qRT-PCR) and western blot were used to analyze the expression of HDAC4 in the clinical samples. siRNA and overexpression of HDAC4 and siRNA p21 were used to study functional effects in a proliferation, a colony formation, a adenosine 5'-triphosphate (ATP) assay and reactive oxygen species(ROS) generation, cell cycle, cell apoptosis rates, and autophagy assays. HDAC4 was up-regulated in gastric cancer tissues and several gastric cancer cell lines. The proliferation, colony formation ability and ATP level were enhanced in HDAC4 overexpression SGC-7901 cells, but inhibited in HDAC4 knockdown SGC-7901 cells. HDAC4 knockdown led to G0/G1 phase cell arrest and caused apoptosis and ROS increase. Moreover, HDAC4 was found to inhibit p21 expression in gastric cancer SGC-7901 cells. p21 knockdown dramatically attenuated cell proliferation inhibition, cell cycle arrest, cell apoptosis promotion and autophagy up-regulation in HDAC4-siRNA SGC-7901 cells. We demonstrated that HDAC4 promotes gastric cancer cell progression mediated through the repression of p21. Our results provide an experimental basis for understanding the pro-tumor mechanism of HDAC4 as treatment for gastric cancer.


Subject(s)
Cyclin-Dependent Kinase Inhibitor p21/genetics , Gene Expression Regulation, Neoplastic , Histone Deacetylases/metabolism , Repressor Proteins/metabolism , Stomach Neoplasms/genetics , Stomach Neoplasms/metabolism , Adenosine Triphosphate/metabolism , Aged , Apoptosis/genetics , Case-Control Studies , Cell Cycle Checkpoints/genetics , Cell Line, Tumor , Cell Proliferation , Histone Deacetylases/genetics , Humans , Middle Aged , Reactive Oxygen Species/metabolism , Repressor Proteins/genetics , Stomach Neoplasms/pathology , Tumor Stem Cell Assay
19.
Neuropharmacology ; 72: 148-56, 2013 Sep.
Article in English | MEDLINE | ID: mdl-23643746

ABSTRACT

The medial prefrontal cortex (mPFC) has been implicated in modulating anxiety. However, it is unknown whether excitatory or inhibitory neurotransmission in the infralimbic (IL) subregion of the mPFC underlies the pathology of anxiety-related behavior. To address this issue, we infused the GABAA receptor (GABAAR) antagonist bicuculline to temporarily activate the IL cortex. IL cortex activation decreased the time spent in the center area in the open field test, decreased exploration of the open-arms in the elevated plus maze test, and increased the latency to bite food in the novelty-suppressed feeding test. These findings substantiate the GABAergic system's role in anxiety-related behaviors. IL cortex inactivation with the AMPA receptor (AMPAR) antagonist CNQX produced opposite, anxiolytic effects. However, infusion of the NMDA receptor (NMDAR) antagonist AP5 into the IL cortex had no significant effect. Additionally, we did not observe motor activity deficits or appetite deficits following inhibition of GABAergic or glutamatergic neurotransmission. Interestingly, we found parallel and corresponding electrophysiological changes in anxious mice; compared to mice with relatively low anxiety, the relatively high anxiety mice exhibited smaller evoked inhibitory postsynaptic currents (eIPSCs) and larger AMPA-mediated evoked excitatory postsynaptic currents (eEPSCs) in pyramidal neurons in the IL cortex. The changes of eIPSCs and eEPSCs were due to presynaptic mechanisms. Our results suggest that imbalances of neurotransmission in the IL cortex may cause a net increase in excitatory inputs onto pyramidal neurons, which may underlie the pathogenic mechanism of anxiety disorders.


Subject(s)
Anxiety/pathology , Excitatory Postsynaptic Potentials/physiology , Prefrontal Cortex/physiopathology , 6-Cyano-7-nitroquinoxaline-2,3-dione/pharmacology , 6-Cyano-7-nitroquinoxaline-2,3-dione/therapeutic use , Animals , Animals, Newborn , Anxiety/chemically induced , Anxiety/drug therapy , Bicuculline/toxicity , Disease Models, Animal , Excitatory Amino Acid Antagonists/pharmacology , Excitatory Amino Acid Antagonists/therapeutic use , Excitatory Postsynaptic Potentials/drug effects , Exploratory Behavior/drug effects , GABA-A Receptor Antagonists/toxicity , In Vitro Techniques , Inhibitory Postsynaptic Potentials/drug effects , Injections, Intraventricular , Male , Maze Learning/drug effects , Mice , Mice, Inbred C57BL , Patch-Clamp Techniques , Prefrontal Cortex/drug effects
20.
PLoS One ; 3(10): e3414, 2008.
Article in English | MEDLINE | ID: mdl-18923708

ABSTRACT

BACKGROUND: Kuntiz-type toxins (KTTs) have been found in the venom of animals such as snake, cone snail and sea anemone. The main ancestral function of Kunitz-type proteins was the inhibition of a diverse array of serine proteases, while toxic activities (such as ion-channel blocking) were developed under a variety of Darwinian selection pressures. How new functions were grafted onto an old protein scaffold and what effect Darwinian selection pressures had on KTT evolution remains a puzzle. PRINCIPAL FINDINGS: Here we report the presence of a new superfamily of ktts in spiders (TARANTULAS: Ornithoctonus huwena and Ornithoctonus hainana), which share low sequence similarity to known KTTs and is clustered in a distinct clade in the phylogenetic tree of KTT evolution. The representative molecule of spider KTTs, HWTX-XI, purified from the venom of O. huwena, is a bi-functional protein which is a very potent trypsin inhibitor (about 30-fold more strong than BPTI) as well as a weak Kv1.1 potassium channel blocker. Structural analysis of HWTX-XI in 3-D by NMR together with comparative function analysis of 18 expressed mutants of this toxin revealed two separate sites, corresponding to these two activities, located on the two ends of the cone-shape molecule of HWTX-XI. Comparison of non-synonymous/synonymous mutation ratios (omega) for each site in spider and snake KTTs, as well as PBTI like body Kunitz proteins revealed high Darwinian selection pressure on the binding sites for Kv channels and serine proteases in snake, while only on the proteases in spider and none detected in body proteins, suggesting different rates and patterns of evolution among them. The results also revealed a series of key events in the history of spider KTT evolution, including the formation of a novel KTT family (named sub-Kuntiz-type toxins) derived from the ancestral native KTTs with the loss of the second disulfide bridge accompanied by several dramatic sequence modifications. CONCLUSIONS/SIGNIFICANCE: These finding illustrate that the two activity sites of Kunitz-type toxins are functionally and evolutionally independent and provide new insights into effects of Darwinian selection pressures on KTT evolution, and mechanisms by which new functions can be grafted onto old protein scaffolds.


Subject(s)
Spider Venoms/pharmacology , Animals , Binding Sites , Evolution, Molecular , Kv1.1 Potassium Channel/antagonists & inhibitors , Protein Conformation , Selection, Genetic , Spider Venoms/chemistry , Spider Venoms/genetics , Spiders , Trypsin Inhibitors
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