Examining the effect of iron (ferric) on physiological processes: Invertebrate models.

Iron is a common and essential element for maintaining life in bacteria, plants and animals and is found in soil, fresh waters and marine waters; however, over exposure is toxic to organisms. Iron is used in electron transport complexes within mitochondria as well as a co-factor in many essential proteins. It is also established that iron accumulation in the central nervous system in mammals is associated with various neurological disorders. Ample studies have investigated the long-term effects of iron overload in the nervous system. However, its acute effects in nervous tissue and additional organ systems warrant further studies. This study investigates the effects of iron overload on development, behavior, survival, cardiac function, and glutamatergic synaptic transmission in the Drosophila melanogaster. Additionally, physiological responses in crayfish were examined following Fe3+ exposure. Fe3+ reduced neuronal excitability in proprioceptive neurons in a crayfish model. Thus, Fe3+ may block stretch activated channels (SACs) as well as voltage-gated Na+ channels. Exposure also rapidly reduces synaptic transmission but does not block ionotropic glutamatergic receptors, suggesting a blockage of pre-synaptic voltage-gated Ca2+ channels in both crustacean and Drosophila models. The effects are partly reversible with acute exposure, indicating the cells are not rapidly damaged. This study is relevant in demonstrating the effects of Fe3+ on various physiological functions in different organisms in order to further understand the acute and long-term consequences of overload.

The Effects of Doxapram Blocking the Response of Gram-Negative Bacterial Toxin (LPS) at Glutamatergic Synapses.

Lipopolysaccharides (LPS) associated with Gram-negative bacteria are one factor responsible for triggering the mammalian immune response. Blocking the action of LPS is key to reducing its downstream effects. However, the direct action of LPS on cells is not yet fully addressed. LPS can have rapid, direct effects on cells in the absence of a systemic immune response. Recent studies have shown that doxapram, a blocker of a subset of K2P channels, also blocks the acute actions of LPS. Doxapram was evaluated to determine if such action also occurs at glutamatergic synapses in which it is known that LPS can increase synaptic transmission. Doxapram at 5 mM first enhanced synaptic transmission, then reduced synaptic response, while 10 mM rapidly blocked transmission. Doxapram at 5 mM blocked the excitatory response induced by LPS. Enhancing synaptic transmission with LPS and then applying LPS combined with doxapram also resulted in retarding the response of LPS. It is possible doxapram and LPS are mediated via a similar receptor or cellular responses. The potential of designing pharmacological compounds with a similar structure to doxapram and determining the binding of such compounds can aid in addressing the acute, direct actions by LPS on cells.

The effects of Gram-positive and Gram-negative bacterial toxins (LTA & LPS) on cardiac function in Drosophila melanogaster larvae.

The effects of Gram negative and positive bacterial sepsis depend on the type of toxins released, such as lipopolysaccharides (LPS) or lipoteichoic acid (LTA). Previous studies show LPS to rapidly hyperpolarize larval Drosophila skeletal muscle, followed by desensitization and return to baseline. In larvae, heart rate increased then decreased with exposure to LPS. However, responses to LTA, as well as the combination of LTA and LPS, on the larval Drosophila heart have not been previously examined. This study examined the effects of LTA and a cocktail of LTA and LPS on heart rate. The combined effects were examined by first treating with either LTA or LPS only, and then with the cocktail. The results showed a rapid increase in heart rate upon LTA application, followed by a gradual decline over time. When applying LTA followed by the cocktail, an increase in the rate occurred. However, if LPS was applied before the cocktail, the rate continued declining. These responses indicate the receptors or cellular cascades responsible for controlling heart rate within seconds and the rapid desensitization are affected by LTA or LPS and a combination of the two. The mechanisms for rapid changes which are not regulated by gene expression by exposure to LTA or LPS or associated bacterial peptidoglycans have yet to be identified in cardiac tissues of any organism.

Bacterial lipopolysaccharide hyperpolarizes the membrane potential and is antagonized by the K2p channel blocker doxapram.

Exposure of Drosophila skeletal muscle to bacterial lipopolysaccharides (LPS) rapidly and transiently hyperpolarizes membrane potential. However, the mechanism responsible for hyperpolarization remains unclear. The resting membrane potential of the cells is maintained through multiple mechanisms. This study investigated the possibility of LPS activating calcium-activated potassium channels (KCa) and/or K2p channels. 2-Aminoethyl diphenylborinate (2-APB), blocks uptake of Ca2+ into the endoplasmic reticulum (ER); thus, limiting release from ryanodine-sensitive internal stores to reduce the function of KCa channels. Exposure to 2-APB produces waves of hyperpolarization even during desensitization of the response to LPS and in the presence of doxapram. This finding in this study suggests that doxapram blocked the acid-sensitive K2p tandem-pore channel subtype known in mammals. Doxapram blocked LPS-induced hyperpolarization and depolarized the muscles as well as induced motor neurons to produce evoked excitatory junction potentials (EJPs). This was induced by depolarizing motor neurons, similar to the increase in extracellular K+ concentration. The hyperpolarizing effect of LPS was not blocked by decreased extracellular Ca2+or the presence of Cd2+. LPS appears to transiently activate doxapram sensitive K2p channels independently of KCa channels in hyperpolarizing the muscle. Septicemia induced by gram-negative bacteria results in an increase in inflammatory cytokines, primarily induced by bacterial LPS. Currently, blockers of LPS receptors in mammals are unknown; further research on doxapram and other K2p channels is warranted. (220 words).

An invertebrate model in examining the effect of acute ferric iron exposure on proprioceptive neurons.

Iron is an essential element for plant and animal life and is found in soil, fresh waters and marine waters. The Fe3+ ion is a vital prosthetic group and cofactor to mitochondrial electron transport complexes and numerous proteins involved in normal functioning. Despite its importance to life-sustaining processes, overexposure results in toxicity. For example, ferric iron (Fe3+) accumulation in the mammalian central nervous system is associated with various neurological disorders. Although current literature addresses the long-term effects of Fe3+ overload, fewer studies exist examining the effects of acute exposure. Using the blue crab (Callinectes sapidus), we investigate the effects of acute Fe3+ overload on proprioception within the propodite-dactylopodite (PD) nerve. For proprioceptive studies, 10- and 20-mM ferric chloride and ferric ammonium citrate solutions were used at 5- and 20- min exposure times. Exposure to 20 mM concentrations of ferric chloride and ferric ammonium citrate reduced excitability in proprioceptive neurons. Thus, Fe3+ likely blocks stretch-activated channels or voltage-gated Na+ channels. The depressive effects of Fe3+ are partly reversible following saline washout, indicating cells are not acutely damaged. Gadolinium (GdCl3, 1 and 10 mM) was used to examine the effects of an additional trivalent ion comparator. Gd3+ depressed PD nerve compound action potential amplitude while increasing the compound action potential duration. This study is relevant in demonstrating the dose-dependent effects of acute Fe3+ and Gd3+ exposure on proprioception and provides a model system to further investigate the mechanisms by which metals act on the nervous system.

The effects of doxapram (blocker of K2p channels) on resting membrane potential and synaptic transmission at the Drosophila neuromuscular junction.

The resting membrane potential of most cells is maintained by potassium K2p channels. The pharmacological profile and distribution of various K2p channel subtypes in organisms are still being investigated. The Drosophila genome contains 11 subtypes; however, their function and expression profiles have not yet been determined. Doxapram is clinically used to enhance respiration in humans and blocks the acid-sensitive K2p TASK subtype in mammals. The resting membrane potential of larval Drosophila muscle and synaptic transmission at the neuromuscular junction are pH sensitive. The present study investigated the effects of doxapram on membrane potential and synaptic transmission using intracellular recordings of larval Drosophila muscles. Doxapram (1 mM and 10 mM) depolarizes the muscle and appears to depolarize motor neurons, causing an increase in the frequency of spontaneous quantal events and evoked excitatory junction potentials. Verapamil (1 and 10 mM) paralleled the action of doxapram. These changes were matched by an extracellular increase in KCl (50 mM) and blocked by Cd2+. It is assumed that the motor nerve depolarizes to open voltage-gated Ca2+ channels in presynaptic nerve terminals because of exposure to doxapram. These findings are significant for building models to better understand the function of pharmacological agents that affect K2p channels and how K2p channels contribute to the physiology of tissues. Drosophila offers a genetically amenable model that can alter the tissue-specific expression of K2p channel subtypes to simulate known human diseases related to this family of channels.

Hyperpolarization Induced by Lipopolysaccharides but Not by Chloroform Is Inhibited by Doxapram, an Inhibitor of Two-P-Domain K+ Channel (K2P).

Bacterial septicemia is commonly induced by Gram-negative bacteria. The immune response is triggered in part by the secretion of bacterial endotoxin lipopolysaccharide (LPS). LPS induces the subsequent release of inflammatory cytokines which can result in pathological conditions. There is no known blocker to the receptors of LPS. The Drosophila larval muscle is an amendable model to rapidly screen various compounds that affect membrane potential and synaptic transmission such as LPS. LPS induces a rapid hyperpolarization in the body wall muscles and depolarization of motor neurons. These actions are blocked by the compound doxapram (10 mM), which is known to inhibit a subtype of the two-P-domain K+ channel (K2P channels). However, the K2P channel blocker PK-THPP had no effect on the Drosophila larval muscle at 1 and 10 mM. These channels are activated by chloroform, which also induces a rapid hyperpolarization of these muscles, but the channels are not blocked by doxapram. Likewise, chloroform does not block the depolarization induced by doxapram. LPS blocks the postsynaptic glutamate receptors on Drosophila muscle. Pre-exposure to doxapram reduces the LPS block of these ionotropic glutamate receptors. Given that the larval Drosophila body wall muscles are depolarized by doxapram and hyperpolarized by chloroform, they offer a model to begin pharmacological profiling of the K2P subtype channels with the potential of identifying blockers for the receptors to mitigate the actions of the Gram-negative endotoxin LPS.

Molecular physiology of manganese in insects.

Manganese is an essential element for maintaining life. Overexposure to the metal, however, can be toxic to organisms. Given the significant function of manganese in insects, agriculture, and human disease, as well as in the healthy ecology of the planet, the biological activities of manganese in insects needs consideration. Because of the role of manganese as a cofactor for essential enzymes present in different organelles, both over and underexposure to manganese has a multifaceted effect on organisms. At the physiological level, the effects of insect exposure to the metal on enzymatic activities and consequent alteration of insect behaviors are best explained through the metal's role in modulating the dopaminergic system. Despite numerous examples that alterations in manganese homeostasis have profound effects on insects, the cellular mechanisms that ensure homeostasis of this essential metal remain presently unknown, calling for further research in this area.

Examining the effect of manganese on physiological processes: Invertebrate models.

Manganese (Mn2+ as MnSO4 &/or MnCl2) is a common and essential element for maintaining life in plants and animals and is found in soil, fresh waters and marine waters; however, over exposure is toxic to organisms. MnSO4 is added to soil for agricultural purposes and people are exposed to Mn2+ in the mining industry. Hypermanganesemia in mammals is associated with neurological issues mimicking Parkinson's disease (PD) and appears to target dopaminergic neural circuits. However, it also seems that hypermanganesemia can affect many aspects of health besides dopaminergic synapses. We examined the effect on development, behavior, survival, cardiac function, and glutamatergic synaptic transmission in the Drosophila melanogaster. In addition, we examined the effect of Mn2+ on a sensory proprioceptive organ and nerve conduction in a marine crustacean and synaptic transmission at glutamatergic neuromuscular junctions of freshwater crayfish. A dose-response effect of higher Mn2+ retards development, survival and cardiac function in larval Drosophila and survival in larvae and adults. MnSO4 as well as MnCl2 blocks stretch activated responses in primary proprioceptive neurons in a dose-response manner. Mn2+ blocks glutamatergic synaptic transmission in Drosophila as well as crayfish via presynaptic action. This study is relevant in demonstrating the effects of Mn2+ on various physiological functions in order to learn more about acute and long-term consequences Mn2+ exposure.

Rapid and Direct Action of Lipopolysaccharide (LPS) on Skeletal Muscle of Larval Drosophila.

The endotoxin lipopolysaccharide (LPS) from Gram-negative bacteria exerts a direct and rapid effect on tissues. While most attention is given to the downstream actions of the immune system in response to LPS, this study focuses on the direct actions of LPS on skeletal muscle in Drosophila melanogaster. It was noted in earlier studies that the membrane potential rapidly hyperpolarizes in a dose-dependent manner with exposure to LPS from Pseudomonas aeruginosa and Serratia marcescens. The response is transitory while exposed to LPS, and the effect does not appear to be due to calcium-activated potassium channels, activated nitric oxide synthase (NOS), or the opening of Cl- channels. The purpose of this study was to further investigate the mechanism of the hyperpolarization of the larval Drosophila muscle due to exposure of LPS using several different experimental paradigms. It appears this response is unlikely related to activation of the Na-K pump or Ca2+ influx. The unknown activation of a K+ efflux could be responsible. This will be an important factor to consider in treatments of bacterial septicemia and cellular energy demands.

Effect of Temperature on Heart Rate for Phaenicia sericata and Drosophila melanogaster with Altered Expression of the TrpA1 Receptors.

The transient receptor potential (TrpA-ankyrin) receptor has been linked to pathological conditions in cardiac function in mammals. To better understand the function of the TrpA1 in regulation of the heart, a Drosophila melanogaster model was used to express TrpA1 in heart and body wall muscles. Heartbeat of in intact larvae as well as hearts in situ, devoid of hormonal and neural input, indicate that strong over-expression of TrpA1 in larvae at 30 or 37 °C stopped the heart from beating, but in a diastolic state. Cardiac function recovered upon cooling after short exposure to high temperature. Parental control larvae (UAS-TrpA1) increased heart rate transiently at 30 and 37 °C but slowed at 37 °C within 3 min for in-situ preparations, while in-vivo larvae maintained a constant heart rate. The in-situ preparations maintained an elevated rate at 30 °C. The heartbeat in the TrpA1-expressing strains could not be revived at 37 °C with serotonin. Thus, TrpA1 activation may have allowed enough Ca2+ influx to activate K(Ca) channels into a form of diastolic stasis. TrpA1 activation in body wall muscle confirmed a depolarization of membrane. In contrast, blowfly Phaenicia sericata larvae increased heartbeat at 30 and 37 °C, demonstrating greater cardiac thermotolerance.

Bacterial endotoxin lipopolysaccharide enhances synaptic transmission at low-output glutamatergic synapses.

The endotoxin lipopolysaccharides (LPS), secreted from gram-negative bacteria, has direct effects on synaptic transmission independent of systemic secondary cytokine responses. High concentration of LPS (500 µg/mL) from Serratia marcescens increased synaptic efficacy at glutamatergic low-output synapses more than for high-output synapses. Over an hour of exposure was not toxic to the preparation and continued to enhance synaptic transmission. A small but significant rapid hyperpolarization of the post-synaptic cells occurred, in addition to a slower enhancement of in the amplitude of evoked excitatory junction potentials. LPS may promote reserve pool vesicles to the readily releasable pool for low-output synapses. The action of LPS at the glutamatergic synapses of the crayfish neuromuscular junction is unique in promoting synaptic transmission as compared to other glutamatergic synapses in Drosophila and mammals, where synaptic transmission is depressed.

The Effect of Bacterial Endotoxin LPS on Serotonergic Modulation of Glutamatergic Synaptic Transmission.

The release of the endotoxin lipopolysaccharides (LPS) from gram-negative bacteria is key in the induction of the downstream cytokine release from cells targeting cells throughout the body. However, LPS itself has direct effects on cellular activity and can alter synaptic transmission. Animals experiencing septicemia are generally in a critical state and are often treated with various pharmacological agents. Since antidepressants related to the serotonergic system have been shown to have a positive outcome for septicemic conditions impacting the central nervous system, the actions of serotonin (5-HT) on neurons also exposed to LPS were investigated. At the model glutamatergic synapse of the crayfish neuromuscular junction (NMJ), 5-HT primarily acts through a 5-HT2A receptor subtype to enhance transmission to the motor neurons. LPS from Serratia marcescens also enhances transmission at the crayfish NMJ but by a currently unknown mechanism. LPS at 100 µg/mL had no significant effect on transmission or on altering the response to 5-HT. LPS at 500 µg/mL increased the amplitude of the evoked synaptic excitatory junction potential, and 5-HT in combination with 500 µg/mL LPS continued to promote enhanced transmission. The preparations maintained responsiveness to serotonin in the presence of low or high concentrations of LPS.

Regional Phenotypic Differences of the Opener Muscle in Procambarus clarkii: Sarcomere Length, Fiber Diameter, and Force Development.

The opener muscle in the walking legs of the crayfish (Procambarus clarkii) has three distinct phenotypic regions although innervated by only one excitatory motor neuron. These regions (distal, central, and proximal) have varied biochemistry and physiology, including synaptic structure, troponin-T levels, fiber diameter, input resistance, sarcomere length, and force generation. The force generated by the central fibers when the excitatory neuron was stimulated at 40 Hz was more than the force generated by the other regions. This increase in force was correlated with the central fibers having longer sarcomeres when measured in a relaxed claw. These data support the idea that the central fibers are tonic-like and that the proximal fibers are phasic-like. The addition of serotonin directly on the fibers was hypothesized to increase the force generated by the central fibers more than in the other regions, but this did not occur at 40-Hz stimulation. We hypothesized that the central distal fibers would generate the most force due to the arrangement on the apodeme. This study demonstrates how malleable the motor unit is with modulation and frequency of stimulation.

The effects of tricaine mesylate on arthropods: crayfish, crab and Drosophila.

Tricaine mesylate, also known as MS-222, was investigated to characterize its effects on sensory neurons, synaptic transmission at the neuromuscular junction, and heart rate in invertebrates. Three species were examined: Drosophila melanogaster, blue crab (Callinectes sapidus), and red swamp crayfish (Procambarus clarkii). Intracellular measures of action potentials in motor neurons of the crayfish demonstrated that MS-222 dampened the amplitude, suggesting that voltage-gated Na + channels are blocked by MS-222. This is likely the mechanism behind the reduced activity measured in sensory neurons and depressed synaptic transmission in all three species as well as reduced cardiac function in the larval Drosophila. To address public access to data, a group effort was used for analysis of given data sets, blind to the experimental design, to gauge analytical accuracy. The determination of a threshold in analysis for measuring extracellular recorded sensory events is critical and is not easily performed with commercial software.

Pharmacological profiling of stretch activated channels in proprioceptive neurons.

Proprioception in mammals and invertebrates occurs through stretch activated ion channels (SACs) localized in sensory endings. In mammals, the primary organs for proprioception are the intrafusal muscle spindles embedded within extrafusal muscle. In invertebrates there are varied types of sensory organs, from chordotonal organs spanning joints to muscle receptor organs (MRO) which are analogous to the mammalian muscle spindles that monitor stretch of muscle fibers. A subset of SACs are the PIEZO channels. They are comprised of a distinct type of protein sequence and are similar among species, from mammals to invertebrates. We screened several new agents (YODA 1, JEDI 2, OB 1 and DOOKU) which have been identified to act on SACs of the PIEZO 1 subtype. JEDI 2 increased activity in the crayfish MRO but not the crab chordotonal organs. The SACs of the crustacean proprioceptors have not been satisfactorily pharmacologically classified, nor has their molecular makeup been identified. We screened these pharmacological agents on model sensory organs in crustaceans to learn more about their subtype classification and compare genomic profiles of related species.

Physiological and Behavioral Indicators to Measure Crustacean Welfare.

This project determined how neural circuits are affected during warming by examining sensory neurons, the neuromuscular junction, and the cardiac function and behavior of the commercially important crustacean species, the red swamp crayfish (Procambarus clarkii). Rapid inactivation of neural function in crustaceans prior to slaughter is important to limit exposure to noxious stimuli, thus improving animal welfare. This study demonstrated that as a crayfish is warmed at 1 °C/min, the heart beat stops at 44 °C. When temperature is rapidly increased, at 44 °C synaptic transmission at the neuromuscular junction ceases and primary sensory neurons stop functioning. Even though animals do not respond to stimuli after being warmed to 44 °C, if sensory neurons are returned to 20 °C saline after two minutes, they may regain function. Conversely, the neuromuscular junction does not regain function after two minutes in 44 °C saline. Examining behavior and heart rate while warming at 1 °C/min, 12 °C/min, or 46 °C/min to 80 °C indicated that at approximately 40 °C the heart rate is altered. Within 10 s at 80 °C, the heart stops with the highest heating rate. Directly placing crayfish in boiling water stopped the heart quickest, within 10 s, which likely represents denaturing of the tissue by heat. Using an impedance measure to detect a heartbeat may also be influenced by movements in the denaturing process of the tissue. A rapid increase in the temperature of the crayfish above 44 °C is key to limit its exposure to noxious stimuli.

Effects of inhibiting mTOR with rapamycin on behavior, development, neuromuscular physiology and cardiac function in larval Drosophila.

Rapamycin and other mTOR inhibitors are being heralded as possible treatments for many human ailments. It is currently being utilized clinically as an immunomodulator after transplantation procedures and as a treatment for certain forms of cancer, but it has numerous potential clinical indications. Some studies have shown profound effects on life cycle and muscle physiology, but these issues have not been addressed in an organism undergoing developmental processes. This paper fills this void by examining the effect of mTOR inhibition by rapamycin on several different qualities of larval Drosophila Various dosages of the compound were fed to second instar larvae. These larvae were monitored for pupae formation to elucidate possible life cycle effects, and a delay to pupation was quantified. Behavioral deficits were documented in rapamycin-treated larvae. Electrophysiological measurements were taken to discern changes in muscle physiology and synaptic signaling (i.e. resting membrane potential, amplitude of excitatory post-synaptic potentials, synaptic facilitation). Pupation delay and effects on behavior that are likely due to synaptic alterations within the central nervous system were discovered in rapamycin-fed larvae. These results allow for several conclusions as to how mTOR inhibition by rapamycin affects a developing organism. This could eventually allow for a more informed decision when using rapamycin and other mTOR inhibitors to treat human diseases, especially in children and adolescents, to account for known side effects.

Effects of bacterial endotoxin on regulation of the heart, a sensory-CNS-motor nerve circuit and neuromuscular junctions: Crustacean model.

Eatable crustaceans are susceptible to bacterial septicemia from injury or a compromised immune defense, which can possibly have detrimental effects in mammals that consume them. Since many crustaceans (i.e., crabs, lobsters and crayfish) are used for animal food and human consumption, it is of interest to understand the effects potential bacterial infections can have on their health as well as ours, including effects on cardiovascular and neuromuscular activities. The Red Swamp crayfish (Procambarus clarkii) was used as a model crustacean to investigate the effect of direct exposure to isolated endotoxin lipopolysaccharide (LPS) and the associated peptidoglycans from gram-negative bacteria (Serratia marcescens). S. marcescens is a common strain identified to cause septicemia in mammals and is prevalently found in nature. LPS injection into the hemolymph of crayfish revealed acute changes in heart rate and effects on survival. Direct LPS exposure on an in situ sensory-CNS-motor circuit produces a decrease in recruiting of the motor nerve at 500 µg/ml but has no significant effect at 100 µg/ml. At the isolated neuromuscular junction, the direct action of the LPS endotoxin (500 µg/ml) enhances evoked synaptic transmission, while not altering facilitation. Also, the amplitude and the frequency of spontaneous vesicle fusion events was not altered by LPS exposure. However, the resting membrane potential of the muscle transiently hyperpolarizes. These direct actions on tissues appear to be independent of innate immune responses and suggest the LPS targets on these tissues have a role in excitability of cellular function. {242 words}.

The Effects of Chloride Flux on Drosophila Heart Rate.

Approaches are sought after to regulate ionotropic and chronotropic properties of the mammalian heart. Electrodes are commonly used for rapidly exciting cardiac tissue and resetting abnormal pacing. With the advent of optogenetics and the use of tissue-specific expression of light-activated channels, cardiac cells cannot only be excited but also inhibited with ion-selective conductance. As a proof of concept for the ability to slow down cardiac pacing, anion-conducting channelrhodopsins (GtACR1/2) and the anion pump halorhodopsin (eNpHR) were expressed in hearts of larval Drosophila and activated by light. Unlike body wall muscles in most animals, the equilibrium potential for Cl- is more positive as compared to the resting membrane potential in larval Drosophila. As a consequence, upon activating the two forms of GtACR1 and 2 with low light intensity the heart rate increased, likely due to depolarization and opening of voltage-gated Ca2+ channels. However, with very intense light activation the heart rate ceases, which may be due to Cl- shunting to the reversal potential for chloride. Activating eNpHR hyperpolarizes body wall and cardiac muscle in larval Drosophila and rapidly decreases heart rate. The decrease in heart rate is related to light intensity. Intense light activation of eNpHR stops the heart from beating, whereas lower intensities slowed the rate. Even with upregulation of the heart rate with serotonin, the pacing of the heart was slowed with light. Thus, regulation of the heart rate in Drosophila can be accomplished by activating anion-conducting channelrhodopsins using light. These approaches are demonstrated in a genetically amenable insect model.