Bio


Dr. Brodt is a Clinical Associate Professor at Stanford University, engaged in clinical care, teaching and research in cardiothoracic anesthesiology. Dr. Brodt is on the SCA Board of Directors and founded the SCA Regional Anesthesia for Cardiothoracic Enhanced Recovery (RACER) Special Interest Group, in addition to serving on multiple SCA committees and task forces. As the recipient of the 2019 SCA-IARS Mid-Career Research Grant, Dr Brodt is pursuing evidence for the utility of regional anesthesia for enhanced recovery in cardiac surgery patients (the RACER study), and continuously seeks to advance the application of regional techniques to a variety of surgical procedures in the population we care for. This stems from a drive to find effective and safe analgesia for cardiac surgery. Dr. Brodt has presented on regional anesthesia for cardiac surgery, considerations for perioperative opioid use, and other topics in cardiac anesthesia at conferences including ASA, SCA, ACA, ERAS Cardiac Society, EACTAIC, moderated the SCA’s first ever international webinar, and is an Editor for the Journal of Cardiothoracic and Vascular Anesthesia. Dr. Brodt is a strong advocate for work-life harmony, and is a proud mom to 4 inspiring children.

Clinical Focus


  • Regional analgesia for cardiac surgery
  • Fast Track Cardiac Surgery
  • Anesthesia for transcatheter and electrophyiology procedures
  • Anesthesiology

Academic Appointments


Administrative Appointments


  • Rotation Director, Stanford Resident Cardiac Anesthesia Rotstion (2017 - 2020)
  • Professional Practice Evaluation Committee, Stanford University (2015 - Present)
  • Clerkship Director, Stanford Hospital Cardiac Anesthesiology Clerkship (2015 - 2018)

Honors & Awards


  • Chief Resident, University of Miami, Department of Anesthesia (2011-2012)
  • Emmanuel M Papper Memorial Award, University of Miami (June 2012)
  • Best Clinical Pearl, Oral Presentation, SCA Thoracic Symposium (April 2013)

Boards, Advisory Committees, Professional Organizations


  • Board of Directors, Society of Cardiothoracic Anesthesiologists (2020 - Present)
  • International Committee, Society of Cardiothoracic Anesthesiologists (2017 - 2021)
  • Online Education Subcommittee, Society of Cardiothoracic Anesthesiologists (2021 - Present)
  • Founding Chair, RACER SIG, Society of Cardiothoracic Anesthesiologists (2020 - 2020)
  • Member, American Society of Anesthesiologists
  • Member, Society of Cardiovascular Anesthesiologists
  • Member, International Anesthesia Research Society
  • Member, California Society of Anesthesiologists

Professional Education


  • Board Certification: National Board of Echocardiography, Advanced Perioperative Transesophageal Echocardiography (2014)
  • Fellowship: University of Miami (2013) FL
  • Residency: University of Miami (2012) FL
  • Internship: University of Miami (2009) FL
  • Medical Education: University of Sydney Medical School (2007) Australia
  • Fellowship, University of Miami, Cardiothoracic anesthesia (ACTA) (2013)
  • Residency, University of Miami, Anesthesiology (2012)
  • Diplomate, National Board of Echocardiography, Advanced Perioperative Transesophageal Echocardiography (2013)
  • Board Certification, American Board of Anesthesiology, Anesthesia (2013)

Current Research and Scholarly Interests


Clinical Education
Regional Anesthesia for Cardiothoracic Enhanced Recovery (RACER)
Anesthesia for transcatheter and electrophyiology procedures

Clinical Trials


  • Regional Anesthesia for Cardiothoracic Enhanced Recovery Not Recruiting

    The erector spinae plane block (ESPB) is a novel regional analgesic technique that provides pain relief with a peripheral nerve block catheter. The goal of this study is to see if bilateral ESPB catheters can improve clinical outcomes in patients undergoing cardiac surgery via sternotomy, such as decreasing the duration of postoperative mechanical ventilation, need for intravenous opioid medications, length of stay in the intensive care unit (ICU), and improving pain scores.

    Stanford is currently not accepting patients for this trial.

    View full details

Graduate and Fellowship Programs


  • Cardiac Anesthesia (Fellowship Program)

All Publications


  • In Response. Anesthesia and analgesia Makkad, B., Heinke, T. L., Sheriffdeen, R., Khatib, D., Brodt, J. L., Meng, M. L., Grant, M. C., Kachulis, B., Popescu, W. M., Wu, C. L., Bollen, B. A. 2023; 137 (6): e52-e53

    View details for DOI 10.1213/ANE.0000000000006708

    View details for PubMedID 37973139

  • Practice Advisory for Preoperative and Intraoperative Pain Management of Cardiac Surgical Patients: Part 2. Anesthesia and analgesia Makkad, B., Heinke, T. L., Sheriffdeen, R., Khatib, D., Brodt, J. L., Meng, M. L., Grant, M. C., Kachulis, B., Popescu, W. M., Wu, C. L., Bollen, B. A. 2023; 137 (1): 26-47

    Abstract

    Pain after cardiac surgery is of moderate to severe intensity, which increases postoperative distress and health care costs, and affects functional recovery. Opioids have been central agents in treating pain after cardiac surgery for decades. The use of multimodal analgesic strategies can promote effective postoperative pain control and help mitigate opioid exposure. This Practice Advisory is part of a series developed by the Society of Cardiovascular Anesthesiologists (SCA) Quality, Safety, and Leadership (QSL) Committee's Opioid Working Group. It is a systematic review of existing literature for various interventions related to the preoperative and intraoperative pain management of cardiac surgical patients. This Practice Advisory provides recommendations for providers caring for patients undergoing cardiac surgery. This entails developing customized pain management strategies for patients, including preoperative patient evaluation, pain management, and opioid use-focused education as well as perioperative use of multimodal analgesics and regional techniques for various cardiac surgical procedures. The literature related to this field is emerging, and future studies will provide additional guidance on ways to improve clinically meaningful patient outcomes.

    View details for DOI 10.1213/ANE.0000000000006506

    View details for PubMedID 37326862

  • Practice Advisory for Preoperative and Intraoperative Pain Management of Thoracic Surgical Patients: Part 1. Anesthesia and analgesia Makkad, B., Heinke, T. L., Sheriffdeen, R., Khatib, D., Brodt, J. L., Meng, M. L., Grant, M. C., Kachulis, B., Popescu, W. M., Wu, C. L., Bollen, B. A. 2023

    Abstract

    Pain after thoracic surgery is of moderate-to-severe intensity and can cause increased postoperative distress and affect functional recovery. Opioids have been central agents in treating pain after thoracic surgery for decades. The use of multimodal analgesic strategies can promote effective postoperative pain control and help mitigate opioid exposure, thus preventing the risk of developing persistent postoperative pain. This practice advisory is part of a series developed by the Society of Cardiovascular Anesthesiologists (SCA) Quality, Safety, and Leadership (QSL) Committee's Opioid Working Group. It is a systematic review of existing literature for various interventions related to the preoperative and intraoperative pain management of thoracic surgical patients and provides recommendations for providers caring for patients undergoing thoracic surgery. This entails developing customized pain management strategies for patients, which includes preoperative patient evaluation, pain management, and opioid use-focused education as well as perioperative use of multimodal analgesics and regional techniques for various thoracic surgical procedures. The literature related to this field is emerging and will hopefully provide more information on ways to improve clinically relevant patient outcomes and promote recovery in the future.

    View details for DOI 10.1213/ANE.0000000000006441

    View details for PubMedID 37079466

  • Pain management and opioid stewardship in adult cardiac surgery: Joint consensus report of the PeriOperative Quality Initiative and the Enhanced Recovery After Surgery Cardiac Society. The Journal of thoracic and cardiovascular surgery Grant, M. C., Chappell, D., Gan, T. J., Manning, M. W., Miller, T. E., Brodt, J. L. 2023

    Abstract

    Opioid-based anesthesia and analgesia is a traditional component of perioperative care for the cardiac surgery patient. Growing enthusiasm for Enhanced Recovery Programs (ERPs) coupled with evidence of potential harm associated with high-dose opioids suggests that we reconsider the role of opioids in cardiac surgery.An interdisciplinary North American panel of experts, using a structured appraisal of the literature and a modified Delphi method, derived consensus recommendations for optimal pain management and opioid stewardship for cardiac surgery patients. Individual recommendations are graded based on the strength and level of evidence.The panel addressed 4 main topics: the harms associated with historical opioid use, the benefits of more targeted opioid administration, the use of nonopioid medications and techniques, and patient and provider education. A key principle that emerged is that opioid stewardship should apply to all cardiac surgery patients, entailing judicious and targeted use of opioids to achieve optimal analgesia with the fewest potential side effects. The process resulted in the promulgation of 6 recommendations regarding pain management and opioid stewardship in cardiac surgery, focused on avoiding the use of high-dose opioids, as well as encouraging more widespread application of foundational aspects of ERPs, such as the use of multimodal nonopioid medications and regional anesthesia techniques, formal patient and provider education, and structured system-level opioid prescription practices.Based on the available literature and expert consensus, there is an opportunity to optimize anesthesia and analgesia for cardiac surgery patients. Although additional research is needed to establish specific strategies, core principles of pain management and opioid stewardship apply to the cardiac surgery population.

    View details for DOI 10.1016/j.jtcvs.2023.01.020

    View details for PubMedID 36868931

  • An Expert Review of Chest Wall Fascial Plane Blocks for Cardiac Surgery. Journal of cardiothoracic and vascular anesthesia Hargrave, J., Grant, M. C., Kolarczyk, L., Kelava, M., Williams, T., Brodt, J., Neelankavil, J. P. 2022

    Abstract

    The recent integration of regional anesthesia techniques into the cardiac surgical patient population has become a component of enhanced recovery after cardiac surgery pathways. Fascial planes of the chest wall enable single-injection or catheter-based infusions to spread local anesthetic over multiple levels of innervation. Although median sternotomy remains a common approach to cardiac surgery, minimally invasive techniques have integrated additional methods of performing cardiac surgery. Understanding the surgical approach and chest wall innervation is crucial to success in choosing the appropriate chest wall block. Parasternal intercostal plane techniques (previously termed "pectointercostal fascial plane" and "transversus thoracic muscle plane") provide anterior chest and ipsilateral sternal coverage. Anterolateral chest wall coverage is feasible with the interpectoral plane and pectoserratus plane blocks (previously termed "pectoralis") and superficial and deep serratus anterior plane blocks. The erector spinae plane block provides extensive coverage of the ipsilateral chest wall. Any of these techniques has the potential to provide bilateral chest wall analgesia. The relative novelty of these techniques requires ongoing research to be strategic, thoughtful, and focused on clinically meaningful outcomes to enable widespread evidence-based implementation. This review article discusses the key perspectives for performing and assessing chest wall blocks in a cardiac surgical population.

    View details for DOI 10.1053/j.jvca.2022.10.026

    View details for PubMedID 36414532

  • Erector spinae plane blocks for cardiac surgery: Are we comparing apples to oranges? Journal of cardiac surgery Bodmer, N. J., Brodt, J. L., Neuburger, P. J. 2022

    View details for DOI 10.1111/jocs.17015

    View details for PubMedID 36218007

  • Buprenorphine and Cardiac Surgery: Navigating the Challenges of Pain Management. Journal of cardiothoracic and vascular anesthesia Fernando, R. J., Graulein, D., Hamzi, R. I., Augoustides, J. G., Khalil, S., Sanders, J., Sibai, N., Hong, T. S., Kiwakyou, L. M., Brodt, J. L. 2022

    View details for DOI 10.1053/j.jvca.2022.04.050

    View details for PubMedID 35667956

  • Continuous Serratus Anterior Plane Block: A Team Approach JOURNAL OF CARDIOTHORACIC AND VASCULAR ANESTHESIA Kim, R. K., Brodt, J., MacArthur, J. W., Tsui, B. H. 2022; 36 (4): 1217-+
  • Perceptions of Gender Disparities Among Women in Cardiothoracic Anesthesiology. Journal of cardiothoracic and vascular anesthesia Methangkool, E., Brodt, J., Kolarczyk, L., Ivascu, N. S., Hicks, M. H., Herrera, E., Oakes, D. 1800

    Abstract

    OBJECTIVE: In this study of women in cardiothoracic anesthesiology, the authors aimed to characterize demographics, roles in leadership, and perceived professional challenges.DESIGN: A prospective cross-sectional survey of female cardiothoracic anesthesiologists in the United States.SETTING: An internet-based survey of 43 questions was sent to women in cardiothoracic anesthesiology. The survey included questions on demographics, leadership, and perceptions of professional challenges including career advancement, compensation, promotion, harassment, and intimidation.PARTICIPANTS: A database of women in cardiothoracic anesthesiology was created via personal contacts and snowball sampling.INTERVENTIONS: None.MEASUREMENTS AND MAIN RESULTS: A total of 153 responses were analyzed, for a response rate of 65.1%. Most respondents were at the Clinical Instructor or Assistant Professor rank. Many women perceived that compensation, promotion, authorship, and career advancement were affected by gender. Furthermore, 67% of respondents identified having children as having a negative impact on career advancement. Many women reported experiencing derogatory comments (55.6%), intimidation (57.8%), microaggression (69.6%), sexual harassment (25.2%), verbal harassment (45.2%), and unwanted physical or sexual advances (24.4%). These behaviors were most often from a surgical attending, anesthesia attending, or patient.CONCLUSION: This survey study of women in cardiothoracic anesthesiology found that many women perceived inequities in financial compensation, authorship opportunities, and promotion; in addition, many felt that their career advancement was impacted negatively by having children. A striking finding was that the majority of women have experienced intimidation, derogatory comments, and microaggressions in the workplace.

    View details for DOI 10.1053/j.jvca.2021.11.015

    View details for PubMedID 34903458

  • Beyond the ventilator-cardiovascular management in SARS-CoV-2 infection INDIAN JOURNAL OF RESPIRATORY CARE Kloosterboer, A. L., Vogelsong, M. A., Brodt, J. L. 2021; 10: 43-49
  • Benefits, Risks, and Challenges of Incisional Analgesia in Pediatric Cardiac Anesthesia. Journal of cardiothoracic and vascular anesthesia Brodt, J. L., Tsui, B. C. 2021

    View details for DOI 10.1053/j.jvca.2021.03.016

    View details for PubMedID 33836960

  • Alternating Side Programmed Intermittent Repeated (ASPIRe) Bolus Regimen for Delivering Local Anesthetic via Bilateral Interfascial Plane Catheters. Journal of cardiothoracic and vascular anesthesia Tsui, B. C., Brodt, J., Pan, S., Caruso, T. J., Kim, R., Horn, J. L., Boublik, J., Tsui, J. H. 2021

    View details for DOI 10.1053/j.jvca.2021.02.036

    View details for PubMedID 33731299

  • Comparison of Postoperative Pain From Catheter Over the Needle (CON) Versus Catheter Through Needle (CTN) Techniques for Erector Spinae Plane Blockade in Patients Undergoing Open Heart Surgery: A Single-Center Retrospective Review. Journal of cardiothoracic and vascular anesthesia Pfaff, K., Brodt, J., Basireddy, S., Boyd, J., Boublik, J., Horn, J., Tsui, B. C. 2020

    View details for DOI 10.1053/j.jvca.2020.11.060

    View details for PubMedID 33342733

  • Opioid-Free Ultra-Fast-Track On-Pump Coronary Artery Bypass Grafting Using Erector Spinae Plane Catheters JOURNAL OF CARDIOTHORACIC AND VASCULAR ANESTHESIA Chanowski, E. P., Horn, J., Boyd, J. H., Tsui, B. H., Brodt, J. L. 2019; 33 (7): 1988–90
  • Cerebral Oximetry Fails as a Monitor of Brain Perfusion in Cardiac Surgery: A Case Report A & A PRACTICE McAvoy, J., Jaffe, R., Brock-Utne, J., Lopez, J., Brodt, J. 2019; 12 (12): 441–43
  • Case Report of an Awake Craniotomy in a Patient With Eisenmenger Syndrome. A&A practice Heifets, B. D., Crawford, E., Jackson, E., Brodt, J., Jaffe, R. A., Burbridge, M. A. 2018; 10 (9): 219-222

    Abstract

    We present a detailed report of an awake craniotomy for recurrent third ventricular colloid cyst in a patient with severe pulmonary arterial hypertension in the setting of Eisenmenger syndrome, performed 6 weeks after we managed the same patient for a more conservative procedure. This patient has a high risk of perioperative mortality and may be particularly susceptible to perioperative hemodynamic changes or fluid shifts. The risks of general anesthesia induction and emergence must be balanced against the risks inherent in an awake craniotomy on a per case basis.

    View details for DOI 10.1213/XAA.0000000000000664

    View details for PubMedID 29708913

    View details for PubMedCentralID PMC6309536

  • Where the Cath Lab and the Pump Room Meet: Anesthesia for Hybrid Procedures. International anesthesiology clinics Brodt, J. L. 2018; 56 (4): 64–73

    View details for PubMedID 30204608

  • Changes in cerebral oxygen saturation during transcatheter aortic valve replacement. Journal of clinical monitoring and computing Brodt, J., Vladinov, G., Castillo-Pedraza, C., Cooper, L., Maratea, E. 2016; 30 (5): 649-653

    Abstract

    Cerebral oxygen saturation (rSO2) is a non-invasive monitor used to monitor cerebral oxygen balance and perfusion. Decreases in rSO2 >20 % from baseline have been associated with cerebral ischemia and increased perioperative morbidity. During transcatheter aortic valve replacement (TAVR), hemodynamic manipulation with ventricular pacing up to 180 beats per minute is necessary for valve deployment. The magnitude and duration of rSO2 change during this manipulation is unclear. In this small case series, changes in rSO2 in patients undergoing TAVR are investigated. Ten ASA IV patients undergoing TAVR with general anesthesia at a university hospital were prospectively observed. Cerebral oximetry values were analyzed at four points: pre-procedure (baseline), after tracheal intubation, during valve deployment, and at procedure end. Baseline rSO2 values were 54.5 ± 6.9 %. After induction of general anesthesia, rSO2 increased to a mean of 66.0 ± 6.7 %. During valve deployment, the mean rSO2 decreased <20 % below baseline to 48.5 ± 13.4 %. In two patients, rSO2 decreased >20 % of baseline. Cerebral oxygenation returned to post-induction values in all patients 13 ± 10 min after valve deployment. At procedure end, the mean rSO2 was 67.6 ± 8.1 %. As expected, rapid ventricular pacing resulting in the desired decrease in cardiac output during valve deployment was associated with a significant decrease in rSO2 compared to post-induction values. However, despite increased post-induction values in all patients, whether related to increased inspired oxygen fraction or reduced cerebral oxygen consumption under anesthesia, two patients experienced a significant decrease in rSO2 compared to baseline. Recovery to baseline was not immediate, and took up to 20 min in three patients. Furthermore, baseline rSO2 in this population was at the lower limit of the published normal range. Significant cerebral desaturation during valve deployment may potentially be limited by maximizing rSO2 after anesthetic induction. Future studies should attempt to correlate recovery in rSO2 with recovery of hemodynamics and cardiac function, provide detailed neurological assessments pre and post procedure, determine the most effective method of maximizing rSO2 prior to hemodynamic manipulation, and provide the most rapid method of recovery of rSO2 following valve deployment.

    View details for DOI 10.1007/s10877-015-9758-8

    View details for PubMedID 26969373

  • Perioperative management of patients with left ventricular assist devices undergoing noncardiac surgery. Annals of cardiac anaesthesia Degnan, M., Brodt, J., Rodriguez-Blanco, Y. 2016; 19 (4): 676-686

    Abstract

    The aim of this study was to describe our institutional experience, primarily with general anesthesiologists consulting with cardiac anesthesiologists, caring for left ventricular assist device (LVAD) patients undergoing noncardiac surgery.This is a retrospective review of the population of patients with LVADs at a single institution undergoing noncardiac procedures between 2009 and 2014. Demographic, perioperative, and procedural data collected included the type of procedure performed, anesthetic technique, vasopressor requirements, invasive monitors used, anesthesia provider type, blood product management, need for postoperative intubation, postoperative disposition and length of stay, and perioperative complications including mortality.Descriptive statistics for categorical variables are presented as frequency distributions and percentages. Continuous variables are expressed as mean ± standard deviation and range when applicable.During the study, 31 patients with LVADs underwent a total of 74 procedures. Each patient underwent an average of 2.4 procedures. Of the total number of procedures, 48 (65%) were upper or lower endoscopies. Considering all procedures, 81% were performed under monitored anesthesia care (MAC). Perioperative care was provided by faculty outside of the division of cardiac anesthesia in 62% of procedures. Invasive blood pressure monitoring was used in 27 (36%) procedures, and a central line, peripherally inserted central catheter or midline was in place preoperatively and used intraoperatively for 38 (51%) procedures. Vasopressors were not required in the majority (65; 88%) of procedures. There was one inhospital mortality secondary to multiorgan failure; 97% of patients survived to discharge after their procedure.At our institution, LVAD patients undergoing noncardiac procedures most frequently require endoscopy. These procedures can frequently be done safely under MAC, with or without consultation by a cardiac anesthesiologist.

    View details for DOI 10.4103/0971-9784.191545

    View details for PubMedID 27716699

  • Ventriculoperitoneal Shunt Insertion Under Monitored Anesthesia Care in a Patient With Severe Pulmonary Hypertension. A & A case reports Burbridge, M. A., Brodt, J., Jaffe, R. A. 2016; 7 (2): 27-29

    Abstract

    A 32-year-old man with severe pulmonary arterial hypertension and Eisenmenger syndrome secondary to congenital ventricular septal defects presented for ventriculoperitoneal shunt insertion. Consultation between surgical and anesthesia teams acknowledged the extreme risk of performing this case, but given ongoing symptoms related to increased intracranial pressure from a large third ventricle colloid cyst, the case was deemed urgent. After a full discussion with the patient, including an explanation of anesthetic expectations and perioperative risks, the case was performed under monitored anesthesia care. Anesthetic management included high-flow nasal cannula oxygen with capnography and arterial blood pressure monitoring, dexmedetomidine infusion, boluses of midazolam and ketamine, and local anesthetic infiltration of the cranial and abdominal incisions as well as the catheter track. Hemodynamic support was provided with an epinephrine infusion, small vasopressin boluses, and inhaled nitric oxide. The patient recovered without any significant problems and was discharged home on postoperative day 3.

    View details for DOI 10.1213/XAA.0000000000000329

    View details for PubMedID 27224039

  • Scleroderma and pulmonary hypertension complicating two pregnancies: use of neuraxial anesthesia, general anesthesia, epoprostenol and a multidisciplinary approach for cesarean delivery INTERNATIONAL JOURNAL OF OBSTETRIC ANESTHESIA Moaveni, D., Cohn, J., BRODT, J., Hoctor, K., Ranasinghe, J. 2015; 24 (4): 375-387

    Abstract

    Literature regarding the anesthetic care of patients with scleroderma during labor and delivery is limited to remote case reports. No recent publications provide information on the anesthetic management of patients with coexisting pulmonary hypertension. This report describes the anesthetic and multidisciplinary management of two pregnant patients with concomitant scleroderma and pulmonary hypertension undergoing cesarean delivery; one with neuraxial anesthesia and one with general anesthesia. Considerations for neuraxial and general anesthesia in patients with concurrent scleroderma and pulmonary hypertension are discussed.

    View details for DOI 10.1016/j.ijoa.2015.08.015

    View details for Web of Science ID 000364255300011

    View details for PubMedID 26119257

  • Orbital Compartment Syndrome Following Extracorporeal Support JOURNAL OF CARDIAC SURGERY Brodt, J., Gologorsky, D., Walter, S., Pham, S. M., Gologorsky, E. 2013; 28 (5): 522-524

    Abstract

    Orbital compartment syndrome (OCS) is a rare, catastrophic, but potentially treatable complication. It requires prompt diagnosis and immediate intervention, as critical period for possible functional recovery is very short. This report adds to our understanding of potential mechanisms of perioperative blindness, and suggests extracorporeal circulatory support, systemic inflammatory response, and massive blood and fluid resuscitation as potential risk factors for perioperative OCS.

    View details for DOI 10.1111/jocs.12196

    View details for Web of Science ID 000324070400013

    View details for PubMedID 23898881

  • Subclavian Vein Catheterization, Chapter 3 Anesthesia Unplugged Brodt, J., Diez, C. McGraw-Hill Professional. 2012; 2
  • The omega-atracotoxins: Selective blockers of insect M-LVA and HVA calcium channels BIOCHEMICAL PHARMACOLOGY Chong, Y., Hayes, J. L., Sollod, B., Wen, S., Wilson, D. T., Hains, P. G., Hodgson, W. C., Broady, K. W., King, G. F., Nicholson, G. M. 2007; 74 (4): 623-638

    Abstract

    The omega-atracotoxins (omega-ACTX) are a family of arthropod-selective peptide neurotoxins from Australian funnel-web spider venoms (Hexathelidae: Atracinae) that are candidates for development as biopesticides. We isolated a 37-residue insect-selective neurotoxin, omega-ACTX-Ar1a, from the venom of the Sydney funnel-web spider Atrax robustus, with high homology to several previously characterized members of the omega-ACTX-1 family. The peptide induced potent excitatory symptoms, followed by flaccid paralysis leading to death, in acute toxicity tests in house crickets. Using isolated smooth and skeletal nerve-muscle preparations, the toxin was shown to lack overt vertebrate toxicity at concentrations up to 1 microM. To further characterize the target of the omega-ACTXs, voltage-clamp analysis using the whole-cell patch-clamp technique was undertaken using cockroach dorsal unpaired median neurons. It is shown here for the first time that omega-ACTX-Ar1a, and its homolog omega-ACTX-Hv1a from Hadronyche versuta, reversibly block both mid-low- (M-LVA) and high-voltage-activated (HVA) insect calcium channel (Ca(v)) currents. This block occurred in the absence of alterations in the voltage-dependence of Ca(v) channel activation, and was voltage-independent, suggesting that omega-ACTX-1 family toxins are pore blockers rather than gating modifiers. At a concentration of 1 microM omega-ACTX-Ar1a failed to significantly affect global K(v) channel currents. However, 1 microM omega-ACTX-Ar1a caused a modest 18% block of insect Na(v) channel currents, similar to the minor block of Na(v) channels reported for other insect Ca(v) channel blockers such as omega-agatoxin IVA. These findings validate both M-LVA and HVA Ca(v) channels as potential targets for insecticides.

    View details for DOI 10.1016/j.bcp.2007.05.017

    View details for Web of Science ID 000248657900009

    View details for PubMedID 17610847