CHARACTERIZING THE PHYSIOLOGICAL ROLE AND TOXICOLOGICAL POTENTIAL OF INSECT K+ ION CHANNELS AND TRANSPORTERS

• Sponsoring Institution: National Institute of Food and Agriculture
• Project Status: COMPLETE
• Funding Source: HATCH
• Reporting Frequency: Annual
• Accession No.: 1010238
• Project Start Date: Jul 30, 2016
• Project End Date: Jun 30, 2020
• Program Code: [(N/A)]- (N/A)

Recipient Organization
LOUISIANA STATE UNIVERSITY
202 HIMES HALL
BATON ROUGE,LA 70803-0100

Performing Department
Entomology

Non Technical Summary
Mosquitoes and ticks are vectors of numerous human diseases that impose enormous health and socioeconomic burdens on much of the developed and developing world. For mosquitoes, the malaria vector, Anopheles gambiae (Ag), and the yellow fever vector, Aedes aegypti (Ae), together are responsible for more than 220,000,000 cases and 600,000 deaths annually. While there have been significant advances in the development of alternative methods (e.g. biologics) for controlling mosquito populations, the mainstay of vector-control programs remains the use of neurotoxic insecticides. Unfortunately, the sustained use of these insecticides over the last several decades has led to the emergence of widespread resistance to these compounds and a reduction in their efficacy for controlling mosquito populations. Consequently, there is an urgent need to identify new molecular targets for insecticide development, but it is imperative to understand the basic physiology of the putative targets prior to employing an insecticide discovery campaign. Therefore, Iwill explore the physiological role a superfamily of K+ ion channels, known as inward rectifying potassium (Kir) channels, and various transporters have in essential insect tissues.Ticks are vectors of a large number of pathogenic microorganisms that cause significant morbidity and mortality within humans and animals. Ticks have accounted for billions of dollarsi n economic loss to agriculturally relevant animals and, similar to mosquitoes, have been selected for extreme insecticide resistance that is limiting effective tick-vectored disease control. Much attention has been given to the tick salivary glands for target sites to control these diseases. These are the site of pathogen ingestion, replication, and dissemination as well as provide salivary proteins essential for pathogen survival after entry into the host. However, the molecular mechanisms of these processes are largely unknown and therefore, an understanding of the physiology of tick salivary glands is important for elucidation of their roles in pathogen dissemination. Intensive research on tick salivary gland transcriptomes and proteomes are in progress or recently completed. Preliminary data suggests there is a range of biologically active components in tick saliva that might serve as putative targets to limit pathogen transmission. It is important to note that this iterative process has been performed for the previous 20 years and little to no advancement or discovery has been accomplished. Therefore, I plan to explore the physiological role of K+ ion channels within the salivary gland, which may serve as putative targets interupt salivation through altering the K+ ion gradient in the polarized epithelial cells.

Animal Health Component

(N/A)

Research Effort Categories

Basic

100%

Applied

(N/A)

Developmental

(N/A)

Classification

Knowledge Area (KA)	Subject of Investigation (SOI)	Field of Science (FOS)	Percent
721	3110	1020	100%

Knowledge Area
721 - Insects and Other Pests Affecting Humans;

Subject Of Investigation
3110 - Insects;

Field Of Science
1020 - Physiology;

Keywords

ion

channel

Goals / Objectives
The ultimate goal of this hatch project is to employ immunohistochemistry, behavioral assays, and neurophysiological studies that will identify the physiological roles that potassium ion channels and potassium-chloride transporters have in the arthropod salivary gland and nervous/muscular systems. This information will provide a platform for subsequent programs to employ insecticide discovery campaigns against these putative targets. InGoal 1, we will test thecentral hypothesisthat Kir channels expressed in the nervous systems are indispensable because they constitute a critical conductance pathway that facilitates theestablishment of K+ gradients and neurotransmitter release, and therefore inhibiting their function will induce neural failure and death. InGoal 2,we will test the hypothesis thation channels, specifically Kir channels, are essential to proper salivary gland function and are critical in the highly intricate physiological processes of insect feeding. InGoal 3, thegoa is to establish a framework of basic physiological data that will provide a platform for future work on the KCC transporter as an insecticide target site.

Project Methods
Goal1 will rely heavily on electrophysiology. Briefly, recordings from the CNS will be performed onthird instar maggots. The CNS will be excised andplaced in physiological saline, and transected inferior to the ventral ganglia as a means to disrupt the blood brain barrier. Next, the central descending nerves will be drawn into a recording suction electrode to record the descending electrical activity emanating from the central nervous system. Signals will be digitized at a rate of 10 Hz and displayed with MacLab Software (ADInstruments). We anticipate that Kir channel block with specific Kir channel inhibitors will induce neural hyperexcitation, which will be noted by an increase in the spike discharge frequency. For neuromuscular junction recordings,the maggot will be pinned and the central nervous system will be removed to eliminate any descending nerve activity. A lateral nerve trunk will be drawn into a suction electrode and electrical stimuli of increasing voltage will be applied to the nerve until a contraction is elicited from a segmental muscle. The contracting muscle will be impaled near the center with a recording microelectrode to record the drug effects on membrane potential and evoked EPSP. All recordings will be digitized as described above. InGoal 2, we will use a number of immunohistochemical assays that will rely on established methods from the core facility located at the LSU vet school. In addition, we will use an established Ramsay assay that is well documented in the literature and has been used by the PI.For Goal3, we will use a similar approach as to the one described inGoal 1.

Progress 07/30/16 to 06/30/20

Outputs
Target Audience:The target audience of this work are academic, industry, and government scientists intersted in novel insecticide design, novel molecular targets for insecticides, and the molecular physiology of K+ ion channels. Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided?This project has provided the opportunity for 3 graduate students to study various portions of insect physiology and insect toxicology. The students have honed their skills on molecular physiology techniques, immunohistochemistry, electrophysiology, co-expression studies, and classic toxicological approaches. How have the results been disseminated to communities of interest?The results have been disseminated through numerous peer-reviewed publications in high impact journals, through multiple presentations at national symposia, and through presentations at large agrochemical companies (e.g. Sumitomo, Corteva). In addition, we have performed outreach events to local high schools to learn neurophysiology. What do you plan to do during the next reporting period to accomplish the goals? Nothing Reported

Impacts
What was accomplished under these goals? We have validated the presence of Kir channels in the insect nervous system through electrophysiology and immunohistochemistry. These data clearly show the presence of Kir channels in the central and peripheral nervous system and our electrophysiology data indicate these channels are accessory to neural function by providing an outlet for spatial buffering. Importantly, inhibition of these channels alters neural function and leads to death. Goal 1 was successfully completed. In goal 2, we have clearly shown that Kir channels constitute an essential conductance pathway for proper function of the arthropod salivary gland and inhibition of Kir conductance with small molecule modulators or genetic ablation results in reduced fluid secretion (flies, mosquitoes, ticks, horn flies, aphids), reduced osmoregulatory capacity (ticks), and inhibition of feeding behavior (flies, mosquitoes, ticks, horn flies, aphids). This goal was successfully completed. Goal 3, we have published 2 papers highlighting the expression patterns, electrophysiological fingerprint, coupling with GABA-gated Cl channels, and toxicological relevance of KCC in flies and mosquitoes. These data provide the first evidence that KCC is a toxicological relevant target site and can be exploited in insecticide development campaigns. Goal 3 was successfully completed. Completion of these goals provides significant evidence Kir channels area critical conductance pathway for proper function of the salivary gland and modulation of these channels reduces sap- or blood-feeding capabilities

Publications

• Type: Journal Articles Status: Published Year Published: 2020 Citation: Zhilin Li, Felicito Guerrero, Adalberto A. Perez de Leon, Lane D Foil, Daniel R Swale. 2020. Small-molecule inhibitors of inward rectifier potassium (Kir) channels reduce bloodmeal feeding of the horn fly, Haematobia irritans. Journal of Medical Entomology. 57(4):1131-1140
• Type: Journal Articles Status: Published Year Published: 2020 Citation: Sarah E. McComic, Leslie C. Rault, Troy D. Anderson, Daniel R Swale. 2020. Reduced neuronal sensitivity and susceptibility of the fall armyworm, Spodoptera frugiperda, to pyrethroids in the absence of known knockdown mutations. Pesticide Biochemistry and Physiology. 169: 104652
• Type: Journal Articles Status: Published Year Published: 2020 Citation: Jennifer R. Williams, Daniel R. Swale, Troy D. Anderson. 2020. Comparative effects of technical and formulated chlorantraniliprole on the survivorship and locomotor activity of the honey bee, Apis mellifera. Pest Management Science. 76(8): 2582-2588

Progress 10/01/18 to 09/30/19

Outputs
Target Audience: The target audience for this research consists of entomologists, toxicologists, and scientists interested in public health. Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided? This project has facilitated the education of five graduate students and two undergraduate students with three graduate student obtaining their masters degree. How have the results been disseminated to communities of interest? The results of this research have been disseminated via papers in refereed journals and presentations at scientific meetings. What do you plan to do during the next reporting period to accomplish the goals? Work on all three goals will continue as components of thesis/dissertation research for three students.

Impacts
What was accomplished under these goals? We have nearly completed the described goals. For Goal 1, we have shown that Kir channel inhibition with small molecule modulators increases the spike discharge frequency of insect central neurons and significantly alters neuromuscular transmission. We have isolated these channels to the subperineural glia and have described a novel pathway for K+ clearance during neural activity. This work is published and a follow-up manuscript will be published in 2020. In Goal 2, we have clearly shown that Kir channels are critical for arthropod salivary gland activity and feeding events and have published their role in the secretory activity and feeding for aphids, ticks, and flies, and a manuscript describing their role in horn fly feeding has been submitted. For goal 3, we have published 2 papers showing KCC constitutes a druggable target site that is critical for neurotransmission and couples to GABA gated chloride channels. Further, we have shown inhibition of these proteins results in mortality.

Publications

• Type: Journal Articles Status: Published Year Published: 2019 Citation: Zhilin Li*, Kevin R. Macaluso#, Lane D Foil#, Daniel R Swale. 2019. Inward Rectifier Potassium (Kir) Channels mediate salivary gland function and blood feeding in the Lone Star Tick, Amblyomma americanum. PLoS Neglected Tropical Diseases (IF: 4.4). 13(2): e0007153
• Type: Journal Articles Status: Published Year Published: 2019 Citation: Zhilin Li*, Jeffrey A. Davis#, Daniel R. Swale. 2019. Chemical Inhibition of Kir channels reduces salivary secretions and phloem feeding of the cotton aphid, Aphis gossypii (Glover). Pest Management Science (IF: 3.2). 75: 2725-2734
• Type: Journal Articles Status: Published Year Published: 2019 Citation: Rui Chen*, Francis J. Prael III, Zhilin Li*, C. David Weaver, Daniel R Swale. 2019. Functional coupling of K+-Cl- Cotransporter to GABA-Gated Cl- Channels in the central nervous system of Drosophila melanogaster leads to altered drug sensitivities. ACS Chemical Neuroscience (IF: 4.3). 10: 2765-2776. Doi: 10.2032/acschemneuro.8b00697

Progress 10/01/17 to 09/30/18

Outputs
Target Audience:Commodity producers, insecticide applicators, researchers, public health officials, insecticide industry Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided?This project has facilitated the education offive graduate students andtwo undergraduate students with one graduate student obtaining his masters degree in May 2018. How have the results been disseminated to communities of interest?Our lab has published 11 peer-reviewed research papers that have a publiation date of 2016-2018, withthree manuscripts currently under review. Our lab has co-authored one review manuscript. Dr. Swale has given 12 invited seminars at universities, industry, or international symposia between 2016-2018. What do you plan to do during the next reporting period to accomplish the goals?We plan to continue characterizing the physiology of Kir channels at the level of the nerve, understand the resistance mitigating potential of KCC, and determine the molecular physology of Kir channels in the insect salivary gland.

Impacts
What was accomplished under these goals? Goal 1: Despite the nervous system being the target tissue of the extreme majority of deployed insecticides, a complete understanding of the physiological pathways critical for proper function of the insect nervous system is still lacking. This fundamental gap pertaining to the foundational neural physiology must be filled to develop a holistic understanding of insect nervous system function that will lead to the development of new insecticides and enhance the utility of model insect systems for mammalian disease research. Therefore, we aimed to highlight the ramifications that chemical and genetic modulation of neural Kir channels has to function of the central nervous system, muscular system, and neuromuscular system through pharmacological and genetic manipulations. Our data provide significant evidence that Drosophila, and likely mosquito, neural systems rely on the inward conductance of K+ ions through Kir channels for proper function since electrophysiological recordings showed dramatic alterations of the CNS spike discharge frequency, broadening and reduced amplitude of the evoked EPSP at the neuromuscular junction, and altered behavior in the adult fly. Based on these data, we conclude that neural Kir channels in insects 1) are critical for proper function of the insect nervous system, 2) represents an unexplored physiological pathway that is likely to shape the understanding of neuronal signaling, maintenance of membrane potentials, and maintenance of the ionic balance of insects, and 3) are capable of inducing acute toxicity to insects through neurological poisoning, which represents a novel mechanism of action with insecticide resistance mitigating potential. Additionally, we have shown that Kir channels are expressed primarily in the glial cells of the fly CNS and not the neurons as previously speculated. Ongoing electrophysiological studies to characterize the role in glial cells is ongoing. Goal 2:Salivary gland secretions are essential for facilitating tick feeding and thus, reducing or preventing saliva secretions into the vertebrate host is likely to reduce feeding and hinder pathogen life cycles. Unfortunately, the epithelial physiology of tick salivary glands and this gap in knowledge obstructs the development of novel therapeutics for inducing cessation of tick feeding.In this study, we characterized the fundamental role of inwardly rectifying potassium (Kir) channel subtypes in tick salivary gland function and provide evidence that pharmacological inhibition of these ion channels reduces the secretory activity of the salivary gland of Amblyomma americanum. The reduced secretory capacity of the salivary gland was directly correlated with a dramatic reduction of blood ingestion during feeding. Further, exposure to modulators of ATP-sensitive Kir (KATP) channels induced mortality to ticks that is likely resultant from an altered osmoregulatory capacity. Interestingly, Drosophila melanogaster fluid ingestion was not altered with KATP modulators, but was significantly reduced with classical Kir channel modulators. Goal 3:GABAergic signaling is the cornerstone for fast synaptic inhibition of neural signaling in arthropods and mammals and is the molecular target for insecticides and pharmaceuticals, respectively. The K+-Cl- cotransporter (KCC) is the primary mechanism by which mature neurons maintain low intracellular Cl- concentration, yet the fundamental physiology, comparative physiology, and toxicological relevance of insect KCC is understudied. Considering this, we employed electrophysiological, genetic, and pharmacological methods to characterize the physiological underpinnings of KCC function to the Drosophila CNS. Our data show that genetic ablation or pharmacological inhibition of KCC results in an increased spike discharge frequency and significantly (P<0.05) reduces the CNS sensitivity to γ-aminobutyric acid (GABA). Further, simultaneous inhibition of KCC and ligand-gated chloride channel (LGCC) complex results in a significant (P<0.001) increase in CNS spontaneous activity over baseline firing rates that, taken together, supports functional coupling of KCC to LGCC function. Interestingly, 75% reduction in KCC mRNA did not alter basal neurotransmission levels indicating that only a fraction of the KCC population is required to maintain Cl- ionic gradient when at rest, but prolonged synaptic activity increases the threshold for GABA-mediated inhibition and reduces nerve sensitivity to GABA. These data expand current knowledge regarding the physiological role of KCC in a model insect and provides the necessary foundation to develop KCC as a novel biochemical target of insecticides as well as complements existing research to provide a holistic understanding of the plasticity in mammalian health and disease.

Publications

• Type: Journal Articles Status: Published Year Published: 2017 Citation: Scott T ONeal, Daniel R. Swale, Jeffrey R. Bloomquist, Troy D. Anderson. 2017. ATP-sensitive inwardly rectifying potassium channel modulators alter cardiac function in honey bees. Journal of Insect Physiology, 99:95-100.
• Type: Journal Articles Status: Published Year Published: 2018 Citation: Rui Chen and Daniel R Swale. 2018. Inwardly rectifying potassium (Kir) channels represent a critical ion conductance pathway in the nervous system of insects. Scientific Reports. 8:1617 DOI:10.1038/s41598-018-20005-z
• Type: Journal Articles Status: Published Year Published: 2018 Citation: Francis J. Prael III, Rui Chen*, Zhilin Li*, Carson W. Reed, Craig W. Lindsey, C. David Weaver, Daniel R Swale. 2018. Use of chemical probes to explore the toxicological potential of the K+/Cl- Cotransporter (KCC) as a novel insecticide target to control the vector of Dengue and Zika virus, Aedes aegypti. Pesticide Biochemistry and Physiology. Special Issue: ACS Proceedings honoring Dr. Jeffrey Bloomquist. 151:10-17. doi: 10.116/j.pestbp.2018.03.019
• Type: Journal Articles Status: Published Year Published: 2018 Citation: Daniel R. Swale, Aaron D. Gross, Quentin R. R. Coquerel, Jeffrey R Bloomquist. 2018. Electrophysiological Recording of the Central Nervous System Activity of Third-Instar Drosophila Melanogaster. Journal of Visualized Experiments (JOVE). (141), e58375, doi:10.3791/58375
• Type: Conference Papers and Presentations Status: Published Year Published: 2017 Citation: Daniel R Swale. 2017. Characterizing potassium transport pathways as novel targets for insecticide design. American Chemical Society  Agrochemical Division. Award Symposium for Jeff Bloomquist, Advances in Insecticide Mode of Action, Chemistry & Resistance.
• Type: Conference Papers and Presentations Status: Published Year Published: 2018 Citation: Daniel R. Swale. 2018. Inward Rectifier Potassium (Kir) Channels: An emerging target for the control of tick populations and tick-vectored pathogens. American Chemical Society, Division of Agrochemicals, Fall National Meeting. Boston, MA, USA.
• Type: Conference Papers and Presentations Status: Published Year Published: 2018 Citation: Daniel R. Swale. 2018. Perspectives to the Identification and Development of New Insecticide Targets. American Chemical Society, Division of Agrochemicals, InsTar Summit, Fall National Meeting. Boston, MA, USA. Invited by. Dr. John Clark

Progress 10/01/16 to 09/30/17

Outputs
Target Audience:Target audience for this project includes a broad range of stakeholders including scientists in academia, government, military, and industry as well as workers in the public health arean. We have collaborated with a number of scientists in academia, industry, and government to broaden the scope of knowledge pertaining to the foundational physiology of arthropod disease vectors and beneficials. Additionally, my lab worked to educate the public on the Zika virus outbreak of 2016. Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided?Thisproject has provided the opportunity totrain a number of graduate students and for me to attend multiple symposia as an invited speaker. How have the results been disseminated to communities of interest?The results have been disseminated through a combination of publications and multiple domestic and international presentations. These presentations have facilitated multiple collaborations and future opportunities. What do you plan to do during the next reporting period to accomplish the goals?We plan to continue course of collecting data and presenting the findings in large symposia to disseminate the results.

Impacts
What was accomplished under these goals? We have collected significant data highlighting the critical role Kir channels serve in the arthropod nervous system and inproviding a mechanism for potassium spatial buffering.We have validated that these channels are critical for a variety of functions within the nervous system, including ionic balance along the axon and neurotransmitter release at the synapse. We have cloned approximately 80% of the open reading frame of the mosquito Kir channel expressed in the nervous system to enable a drug discovery approach. We have shown that Kir channels represent a critical conductance pathway that is required for feeding in a variety of arthropods. Previously, we had just characterized the fly salivary glands, but have expanded this study to multiple species of flies, mosquitoes, aphids, and ticks. We have tested and confirmed the hypothesis that these channels are important for salivation and feeding. These data provide significant fodder for publicatoin and subsequent grant proposals. Lastly, we have employed various human KCC inhibitors to test the hypotheis that KCC represents a putative target site for mosquito control. Indeed, lethality was observed after mosquiotes were exposed to the molecule and signs of intoxcation are in line with neural poisonining. Due to this, we have cloned the open reading frame, developed a cell line, and established an in vitro screening platform capable of identifying insect selective modulators.

Publications

• Type: Journal Articles Status: Accepted Year Published: 2018 Citation: Daniel R Swale, Jake Z Kraft, Zhilin Li, Kristen-Bartlett Healy, Mei Liu, Zhijun Liu, Lane D Foil. 2017 (accepted). Development of an autodissemination strategy for the deployment of novel control agents targeting the Common Malaria Mosquito, Anopheles quadrimaculatus. PLoS: Neglected Tropical Diseases.
• Type: Journal Articles Status: Under Review Year Published: 2018 Citation: Rui Chen and Daniel R Swale. 2017 (in reivew, Nov 2017). Inward rectifying potassium channels represent a critical conductance pathway in the nervous system of insects. Scientific Reports.
• Type: Journal Articles Status: Submitted Year Published: 2018 Citation: Francis Patel, Rui Chen, Zhilin Li, Craig W Lindsley, C. David Weaver, Daniel R Swale. 2017 (Submitted). Employing VU0463271 to probe the toxicological potential of the K+/Cl- Cotransporter (kcc) as a novel insecticide target to control the vector of Dengue and Zika virus, Aedes aegypti. Pesticide Biochemistry and Physiology
• Type: Journal Articles Status: Published Year Published: 2017 Citation: Scott T. ONeal, Daniel R Swale, Troy D. Anderson. 2017. ATP-sensitive inwardly rectifying potassium channel regulation of viral infections in honey bees. Scientific Reports. 7(1):8668. doi: 10.1038/s41598-017-09448-y
• Type: Journal Articles Status: Published Year Published: 2017 Citation: Scott T ONeal, Daniel R. Swale, Jeffrey R. Bloomquist, Troy D. Anderson. 2017. ATP-sensitive inwardly rectifying potassium channel modulators alter cardiac function in honey bees. Journal of Insect Physiology, 99:95-100.

Progress 07/30/16 to 09/30/16

Outputs
Target Audience:The target audience of this year's work was scientists in the fields of neurophysiology, neuropharmacology, and vector-borne disease control Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided?This Hatch project has provided multiple invited and volunteered presentations at international and national symposia. A total of 13 presentations were given at meetings in 2016. The attendance at thesepresentation has facilitated the development of multiple collaborations withuniversities and governmental agencies. How have the results been disseminated to communities of interest?We have published three papers in 2016 through peer-reviewed journals that are internationally recognized. We have also given a total of 15 presentations or semiars to disseminate the collected data. What do you plan to do during the next reporting period to accomplish the goals?We plan to continue course of collecting data and presenting the findings in large symposia to disseminate the results.

Impacts
What was accomplished under these goals? We have collected significant data highlighting the critical role Kir channels serve in the arthropod nervous system and provide a mechanism for potassium spatial buffering. Furthermore, these channels appear to play a role in neurotranmitter release from the presynaptic terminal and/or postsynaptic terminal responsiveness. A student is arriving January 2017 and will complete this data set and we expect publication in Fall 2017. We have published a proof-of-concept manuscript that highlights the critical role Kir channels serve in arthropod salivary gland function and shows they are essential for sucrose feeding.Furthermore, we have begun to elucidate the role of these channels in the intricate process of mosquito blood feeding and have identified a number of unique findings that provide significant fodder for subsequent publications and grant funding.

Publications

• Type: Journal Articles Status: Accepted Year Published: 2016 Citation: Daniel R Swale, Zhilin Li, Adalberto A Perez de Leon, Felicito Guerrero, Lane Foil. Inward rectifying potassium channels expressed in the Drosophila melanogaster salivary gland are necessary for proper feeding. Pesticide Biochemistry and Physiology. Accepted October 2016
• Type: Journal Articles Status: Published Year Published: 2016 Citation: Daniel R. Swale, Darren W. Engers, Sean R. Bollinger, Aaron Gross, Edna Alfaro Inocente, Emily Days, Fariba Kanga, Reed M. Johnson, Liu Yang Jeffrey R. Bloomquist, Corey R. Hopkins, Peter M. Piermarini, Jerod S. Denton. 2016. An insecticide resistance-breaking mosquitocide targeting inward rectifier potassium channels in vectors of Zika virus and malaria. Scientific Reports. 6:36954. DOI: 10.1038/srep36954
• Type: Journal Articles Status: Published Year Published: 2016 Citation: Daniel R. Swale, Haruto Kurato, Sujay Kharade, Johnathan Sheehan, Rene Raphemot, Karl Voigtritter, Eric Figueroa, Jens Meiler, Anna Flobaum, Craig Lindsley, Corey Hopkins, Jerod S. Denton. 2016. ML418: The first selective, sub-micromolar pore blocker of Kir7.1 potassium channels. ACS Chemical Neuroscience (IF: 4.4). 7: 1013-1023. DOI: 10.1021/acschemneuro.6b00111
• Type: Conference Papers and Presentations Status: Accepted Year Published: 2016 Citation: Daniel R. Swale. 2016. Of Mosquitoes and Men: Blurring the Lines Between Mammalian and Insect Physiology for the Development of Insecticide Targets. Pathobiological Sciences / Comparative Biomedical Sciences Seminar Series. LSU Veterinary Medicine, Baton Rouge, LA. (Invited By: Dr. Michael Mathis)
• Type: Conference Papers and Presentations Status: Accepted Year Published: 2016 Citation: Daniel R. Swale. 2016. Exploring the physiological role and toxicological potential of the insect K+/Cl- Cotransporter (KCC). Society of Vector Ecology (SOVE). Anchorage, AK. Invited By: Dr. Ulrich Bernier
• Type: Conference Papers and Presentations Status: Accepted Year Published: 2016 Citation: 4. Daniel R. Swale. 2016. Identification and physiological characterization of inward rectifying potassium channels in the arthropod salivary gland. International Award Symposium for Professor Yoshihisa Ozoe, National Meeting of the American Chemical Society  Agrochemical Division, Philadelphia, PA, August 2016.
• Type: Conference Papers and Presentations Status: Accepted Year Published: 2016 Citation: Daniel R. Swale. 2016. Characterization of inward rectifying potassium channels in the salivary glands of arthropod disease vectors. The 26th International Congress of Entomology (ICE), Section: Physiology and Biochemistry, Orlando, FL, September, 2016.
• Type: Conference Papers and Presentations Status: Accepted Year Published: 2016 Citation: Daniel R. Swale. 2016. Novel approaches for malaria control: exploiting potassium ion channels and insect growth regulators in attract and kill strategies. International Centre for Insect Physiology and Ecology. Nairobi, Kenya. February 2016. Invited by Dr. James Mutunga
• Type: Conference Papers and Presentations Status: Accepted Year Published: 2016 Citation: Daniel R Swale, Kristen Healy, Emily Boothe, Randy Vaeth, Todd Walker. 2016. Using the horizontal transfer capabilities of insect growth regulators to control population levels of the Malaria mosquitoes, Anopheles gambiae and Anopheles quadrimaculatus. Society of Vector Ecology (SOVE). Anchorage, AK, USA. September 2016.
• Type: Conference Papers and Presentations Status: Accepted Year Published: 2016 Citation: Scott ONeal, Daniel R. Swale, Jeffrey R Bloomquist, Troy D Anderson. Cardiac regulation of viral infection in a model social insect. 26th International Congress of Entomology (ICE), Orlando, FL, September, 2016
• Type: Conference Papers and Presentations Status: Accepted Year Published: 2016 Citation: Zhilin Li, Daniel R. Swale. Characterization of Physiological Role of Potassium Ion Channels in the Arthropod Salivary Gland. 26th International Congress of Entomology (ICE), Orlando, FL, September, 2016
• Type: Conference Papers and Presentations Status: Accepted Year Published: 2016 Citation: Devika Bhalerao, Daniel R. Swale, Lane Foil, Claudia Husseneder. Determining bioindicators for the impact of oil spills using the food web of larvae of the greenhead horse fly (Tabanus nigrovittatus). The 26th International Congress of Entomology (ICE), Orlando, FL, September, 2016