You are in: eMedicine Specialties > Critical Care > MEDICAL TOPICS Toxicity, Cone Shell NeurotoxinArticle Last Updated: Mar 12, 2008AUTHOR AND EDITOR INFORMATIONSection 1 of 9
  Author: Don R Revis Jr, MD, Consulting Staff, Department of Surgery, Division of Plastic and Reconstructive Surgery, University of Florida College of Medicine Don R Revis, Jr, is a member of the following medical societies: American College of Surgeons, American Medical Association, American Society for Aesthetic Plastic Surgery, and American Society of Plastic Surgeons Editors: Steven R Gambert, MD, Program Director, Physician-in-Chief, Professor, Department of Internal Medicine, Sinai Hospital, Johns Hopkins University School of Medicine; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; Daniel R Ouellette, MD, FCCP, Associate Professor of Medicine, Wayne State University School of Medicine; Consulting Staff, Pulmonary Disease and Critical Care Medicine Service, Henry Ford Health System; Timothy D Rice, MD, Associate Professor, Departments of Internal Medicine and Pediatrics and Adolescent Medicine, Saint Louis University School of Medicine; Michael R Pinsky, MD, CM, Professor of Critical Care Medicine, Bioengineering, Cardiovascular Diseases and Anesthesiology, University of Pittsburgh School of Medicine, University of Pittsburgh Medical Center Author and Editor Disclosure Synonyms and related keywords: cone shell neurotoxin, Conidae, marine snails, molluscs, mollusks, Conus geographus, C geographus, alpha-conotoxins, alpha-neurotoxins, omega-conotoxins, mu-conotoxins, delta-conotoxins, kappa-conotoxins, conantokins, neurotoxin, cone shell, cone shell toxin, mollusk toxin, conotoxin INTRODUCTIONSection 2 of 9
  BackgroundCone shells, members of the family Conidae, are marine snails prized for their beautiful, intricately designed shells. However, these molluscs also produce potent neurotoxins and sting when disturbed. Cone shells are found in the Indo-Pacific region and along the southern Australian coast. They usually live in intertidal regions, where they are easily found among the rocks and corals exposed at low tide, but they have also been found in waters as deep as 30 meters. The species within the Conidae family have various diets, including fish (piscivorous cones), worms (vermivorous cones), and other molluscs (molluscivorous cones). To survive, these rather slow-moving creatures have developed an array of potent neurotoxins to immobilize much faster prey. It is believed that the cone shell detects its prey primarily with chemoreceptors that continually monitor its environment, although some visual signals might also be involved. The cone shell extends its proboscis, on the end of which is a hollow, poison-filled barbed tooth. The intended prey is harpooned with this tooth, which then conveys the potent toxins. The cone shell remains attached to the prey via a thread trailing from the tooth to the snail. Once paralyzed, the prey is drawn in by the thread, and the cone shell ingests it. The cone shell can "reload" for multiple envenomations if necessary. PathophysiologyNeuronal communication is a complex interaction of chemical signals that allows cells to communicate with each other via neurotransmitters. At the neuromuscular junction in skeletal muscle, the arrival of an action potential propagated through the nervous system causes the activation of calcium ion channels, resulting in exocytosis of acetylcholine from vesicular stores within the terminal axon or motor endplate. Acetylcholine then diffuses across the neuromuscular junction to bind to acetylcholine receptors of the muscle endplate. Activation of this receptor induces a conformational change that allows the influx of sodium and calcium into the muscle. This influx of cations causes depolarization of the membrane, activation of voltage-gated ion channels for sodium and calcium, and muscle contraction. Muscle contractions are coordinated and propagated in this manner. The neurotoxins possessed by the cone shell are small peptides of fewer than 30 amino acids, which target different aspects of this neuronal communication sequence to achieve a common result, paralysis. Through this interaction, the cone shell succeeds in paralyzing its prey for subsequent ingestion. Alpha-conotoxins have the same mechanism of action as the alpha-neurotoxins from snake venom; specifically, they bind to and inhibit the acetylcholine receptor. The neurotoxins of some species, such as Conus geographus, are selective for the muscle-type acetylcholine receptor, while the neurotoxins of other species are selective for the neuronal-type acetylcholine receptor. Binding to the muscle-type receptor causes postsynaptic inhibition at the neuromuscular junction, leading to paralysis and death. These symptoms are similar to those caused by curare poisoning and ultimately result in respiratory failure. Omega-conotoxins act to block voltage-gated calcium channels and also block conduction at the neuromuscular junctions of skeletal muscles. A member of this toxin family, omega-conotoxin MVIIA (also known as SNX-111), is reportedly useful as a nonaddictive analgesic up to 1000 times more potent than morphine. Mu-conotoxins act to block voltage-gated sodium channels in muscles and, to a very limited extent, within neurons. Delta-conotoxins also act to block the voltage-gated sodium channel. Kappa-conotoxins and conantokins act to block voltage-gated potassium channels. The specificity with which conotoxins bind to certain receptors has led to their use in studying the molecular biology of receptor interactions. When envenomations occur in humans, usually to the hands or feet, the result is somewhat unpredictable. Minor envenomations cause pain, swelling, and localized numbness that often subside within hours of onset. Serious envenomations are associated with a rapid progression of symptoms, including paralysis, respiratory arrest, cardiac failure, and death. FrequencyUnited StatesCone shells are not indigenous to US waters, but travelers should be aware of them. InternationalThirty cases of human envenomation have been recorded from the Indo-Pacific region and Australia. Mortality/MorbiditySeverity of illness varies among species, with C geographus possessing the most potent toxins. Some individuals have experienced mild symptoms of numbness for only a few hours, while others have died after a short course of rapidly progressive respiratory failure. CLINICALSection 3 of 9
HistoryNote the time of injury and collect the cone shell for identification if it is possible to do so safely. Patients usually report an unexpected stinging pain in the hands or feet while deliberately or unknowingly encountering a cone shell during diving or reef walking.
PhysicalCheck ABCs and vital signs as with any acutely ill patient.
CausesEnvenomations typically occur from mishandling of live specimens in one of the following scenarios:
DIFFERENTIALSSection 4 of 9
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