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Class Lecture Notes 2-13 - Jan 9-Feb 4 - PSYCH 2NF3.docx

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McMaster University
Gautam Ullal

Psych 2NF3 2013 Lecture 112 Jan 9Feb 4 Ion Channels and Neuronal Activity Nature is nowhere accustomed more openly to display her secret mysteries than in cases where she shows traces of her workings apart form the beaten path nor is there any better way to advance the proper practice of medicine than to give our minds to the discovery of the usual law of nature by careful investigation of cases of rarer forms of diseaseWilliam Harvey 15781657Vignette 1 A Case of Eating Sashimi Fugu Puffer FishAs part of his celebration for graduating from the University in Japan Hironori had a dinner with his other Japanese friends in a special sushi restaurant that serves exotic sashimiThis dish he ordered specially for himself was called Sashimi FuguAlong with that he had some rice and a cup of sakeWithin few minutes as he was having his dinner abHironori started feeling lightheadedHis lips started feeling funny He seemed to enjoy the experience By the time his ccfriends realized what was happening he became unresponsive to their calls and slumped on the dinner tableHis limbs deshowed a rapidly progressive ascending paralysis Very soon he started gasping for breath The attending restaurant staff was alerted Paramedic services were called while respiratory resuscitation measures were being offered The blood fpressure dropped rapidly There was an atmosphere of great concern Immediately on entering the hospital blood and gurine samples were taken for mass spectrometry a Light HeadedDizzySake could produce dizziness alcohol intoxication b ParesthesiaFeeling FunnyTingling SensationsNumbnessOccurs when sensory nerve fibers are involvedThesiasensationEg When sitting for a long time c Slumpeddropped d Ascending Paralysisparalysis of muscles starting with lower part of the body spreading upwardsmotor nervous system is affectedFunny feeling started in lips top but paralysis was ascending bottom to top o Probably because nerve channels in lower limbs are more prone to this effect o Probably started in oral cavity because it was the first place of absorption e Gasping for breathbecoming breathlessrespiratory muscles are affectedf Drop in blood pressure is often associated with autonomic nervous system involvement g Mass spectrometry of urine is often required to diagnose tetrodotoxinpoisoningUrine samples have to be taken immediatelyAgendaAnalyzing Case Studies 1 Analyze the vignette special characteristics of Sashimi FuguSashimi made of puffer fish Tetraodontidaedont need to know namePuffer fish contains one of the most poisonous vertebratetoxinsTetrodotoxin TTXTTX is concentrated in liver gonads gut and skin of the fishTTX effectively blocks Na channel permeability at the rising phase of the action potential in the central and peripheral nervesConsumed for its reputation of causing lightheadednessproblems arise when dosage goes higher than it shouldGreat caution and skill require while preparing the particular sashimiSpecial legal license required to prepare sashimi fuguOnly supportive treatmentno specific treatment2 Tetradotoxintoxin blocks sodium channels1mg of TTX can kill an average adult humanTTX is not synthesized by the puffer fish puffer fish is a host for symbiotic bacteria that synthesize itSingle point mutation in the Na ion channel in the puffer fish makes the channels resistant to TTXDifferent Na channels in humans have different levels of sensitivity to TTX o Eg Cardiac muscle skeletal muscle Na channels are resistant o Paralysis occurs not because Na channels on muscles are blockedit is the neuron that stimulates the muscle that is blockedGrade of poisoning with TTX progressive levelso Perioralaround the lips 1 Psych 2NF3 2013o Lingualtongue o Distalterminal anatomical regions of the body such as fingers and toeso Flaccid Paralysismuscles that are paralyzed are flabby there is no tension in the musclesLack of tone o Aphoniainability to produce sound in the voiceWeakness in voice Motor Nerves Sensory Nerveso Hypoxialack of oxygen o Hypotensionlow blood pressure o Cardiac dysrhythmiairregular heartbeat o Unconsciousness may occur due to lack of oxygen to the brainNeurophysiology of TTX Poisoning o As late as 24hours after TTX poisoning a study four in four patientso Greater effect of TTX on amplitude of responses in sensory nerves o Increase in latencyLatencytime required for response high latencylonger time o Low does of TTX used to treat pain o Neuropathicdamaged neurons that causes pain various causes o BlueControl o RedTTXTTX tightly blocks voltagegated Na channels of neuronal membraneIt masquerades as a hydrated Na ion thereby gaining access to the Na ion channel and attaches to itHydrated Na ion also attached to the sodium channel but very transiently nanosecondsTTX binds for several seconds thus preventing Na entry 3 Ion Channels Why have them a To selectively conduct various ions across cell membranesexcite conduct b Vary the excitability of the cell based on various external and internal signals eg voltage chemicalsVarious types of channelssome respond to light temperature neurotransmitters 4 Ion Channels TypesGatedall these channels are more significant for action potentials and transmission of nerve impulses a Voltage Gatedregulated by voltage changesEg Axon hillock high density channels along axon sensitive to change b Ligand Gatedregulated by chemical transmitters ions second messengers eg cyclic GMP etc2 Psych 2NF3 2013Eg dendritic terminals with neurotransmitterreceptor gated channelLigandchemical substance that activates a channel or a receptorEg neurotransmitter mediated Ca mediated o NOTEjust because channel is opened doesnt mean any molecule can enterc Mechanically Gatedregulated by stretch vibration etcEg Stretch receptors in muscles and skin hair cells of internal ear Muscle Spindle Hair Cells Stretch receptors in muscle spindle sends impulses to spinal cord d LightPhoton Gatedregulated by photons Eg channel rhodopsin of retinaEg rod and cone receptors of retinaChemical rhodopsine Temperature GatedEg thermal receptors in skin Free Nerve Endings3
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