Mini Episode: The Saga of the Cardiac Action Potential

Hey everyone, this is a pre-roll announcement. It's going to take exactly 5 minutes and because I really want to get the word out, it's in front of almost every episode. Now you know because I value your time, in my intros I always give you time stamps, so you could jump forward in the episode to whatever interests you most. But if you're listening to this message, it means there's 5 minutes that I inserted in front of it. So add 5 minutes to whatever I said in the intro and it should take you there. If you've heard this announcement, feel free to skip ahead, but if you have not, I promise you're going to want to listen. Here we go. Hey everyone, it's Ryan from The Poison Lab with an announcement I am beyond excited to share. After ages of tinkering, testing, and refining, my poisonous mushroom card game is finally here. Gotta pick 'em. You can get your copy at gottapickum.com and click the link that says "buy gotta pick 'em". The game is so much fun and it's actually pretty educational. The name of the game itself, gottapickum, is a pneumonic to help remember the poisonous mushrooms. And you can find a podcast episode about that at thepoisonlab.com. Check out the episode, a pneumonic for poisonous mushrooms with Dr. Rob Bassett to learn more. But we're talking about the game, which contains 58 individual poisonous mushrooms, as well as 19 different antidotes or modifier cards. You get dealt to hand of different mushrooms and antidotes and you can forage one of them. Then you pass your hand to the next player and get a new hand from someone else. You score points by collecting mushrooms within the same toxin class, grabbing their antidotes, or modifiers that make the mushrooms more or less toxic. So as you forage, you can build strategies to get more points from the same mushrooms in the next rounds. It's a bit of an engine builder meets sushi go. And because I'm a huge nerd, the scoring systems actually complement the toxins, where the things that cause late toxicity get you points later, chronic toxicity builds up over time, which actually 15 different ways to score. It's really fun. And it's endlessly replayable. Not only do you get different hands every game, which might change your strategy, but in between rounds you change up how things are scored by drawing bonus cards, which might get you extra points for say a mushroom that has a ring on this type, or mushrooms with a certain color spore print, or a certain toxin class. All in all, there are 34 different bonus cards. On top of that, at www.gottapicum.com, you can find multiple rule variations to change up the way you play, and you can experiment and find the way you like the most. And at gottapicum.com, you can find several different links to companion blogs that will help you learn while you play. Click Learn the Numeric to learn about the gottapicum numeric and how it characterizes the different toxic mushrooms. Or click Learn Basics about Identification to find the blog that will run you through mushroom anatomy and ID to help you understand what features are listed on the card. And most importantly, definitely check out the Learn the Mushrooms link to find the companion blog with pictures of all of the mushrooms from the cards and a detailed explainer for each toxin class where they're found, the toxic syndrome that they create, how they're treated, real case reports of poisoning from those mushrooms and expert insights. Because this game about poisonous mushrooms was made by people who treat poisonous mushrooms. So whether you're a poison nerd, a mushroom nerd, or a board game enthusiast, this game is made for you. Head over to gottapicum.com and you can get a copy of it for yourself. I cannot wait for you to play this and please nothing would make me happier to see a picture of you playing your first round. So please snap a photo and send it to Tox Talk 1, T-O-X-T-A-L-K-1 at gmail.com. I'm really excited for you to check this out. I know I have a blast playing it and I think you will too. And remember buying this game is not the only way you can show support for the show. This is a totally unfunded production and it exists because of support from listeners like you to help pay for website hosting, audio production software, sound engineers, all sorts of hidden costs that are associated with putting on an educational show like this. So you can help support the show at www.thepoisonlab.com/support and you'll get something back. Not only will you have no ads while you're listening as well as bonus content but supporting members actually had early access to buying this game at a discounted price. And they're enrolled for things like giveaways of this game or merch when we have it available. So if you want ad free episodes, bonus content, updates as soon as possible and access to things like giveaways or discounts when they're available, head over to www.thepoisonlab.com/support. For as little as a dollar a month you can help us keep the show going. But you don't have to pay anything to support the show. I'm just happy you're here listening. Thank you for being part of the community that makes this show so much fun. Welcome to the mini episode. If you're listening it's because you want to know a little bit more about the cardiac conduction cycle and how exactly low paramide is capable of producing an arrhythmia known as torsots. As we had mentioned in the initial episode, low paramide doesn't really kill people the same way other opioids do. The toxicity of a paramide seems to manifest as cardiac arrest from an arrhythmia known as torsols the pomp. Which is French for twisting of points. Which is the pattern that we usually see on an EKG from somebody in this rhythm. And low paramide is not the only drug that causes this arrhythmia. There's other things, methadone, anti-rhythmic, like doffetalide. They can all cause it too. And when we start someone on one of those drugs we get serial EKGs just to evaluate the risk of this effect. But if you are taking unsupervised quantities of this drug you are quite likely to go into an arrhythmia. So how can I teach you about arrhythmia without boring you out of your mind talking about cardiac action potentials? Which actually as an aside I think are very interesting. But I do understand I get a lot of glazed over looks when I start talking about them. Well I'm going to have to get a little creative. We're going to use a story to make things a little bit easier to digest. And we'll review some of the basic concepts of arrhythmia propagation. Now if you have a medical or science background and let's say you already know what say a funny type sodium channel is or that phase two of depolarization is calcium entering the cell. Well then you might want to listen to the other episode which goes pretty heavily in depth into cardiac action potentials early after depolarizations and different mechanisms like rantr and rhythms that propagate torsons. But for everyone else this is going to be a more fun and easily a digestible way to understand the toxic mechanisms of potassium channel blockers and causing torsons. So let's dive in. Before we jump into our story we have to understand how the heart actually works. And as we said before I want you to think of the heart like a light bulb and each time the heart beats it's like turning the light on. Well if the light only turned on once you would only ever have one heart beat and that's not very conducive to life. So in order to have another heart beat I need it to turn off. So it can turn on again. And the way that it does this is moving charge particles called ions specifically sodium potassium and calcium through the cell in a specific order. The order it moves through the cell is called the cardiac action potential. And it has to happen in a very specific sequence for everything to work out appropriately. So to explain the order of the cardiac action potential how it turns on and then resets itself without making your eyes go glossy we're going to tell a little story. A story of a battle as old as time and as integral as good and evil. If this battle were ever stopped being waged life itself would cease. We are telling the story of the siege of castle myocyte. So there's this castle myocyte which is a heart so actually there's about two billion of these castles but they all are doing the same things. And in this castle live the noble lords of calcium and the nation of sodium. Both great and noble people who have lived there for I don't know millennia. But one day a new tribe of lords show up. And those are the people of potassium. The people of potassium are a rich and powerful but malevolent family. They want to live in the castles but there's not enough room so they begin to pay mercenaries in gold to start taking the nation of sodium and kicking them out of the castle. Now in this realm the gold or currency is something called ATP, an energy molecule. The mercenaries drink it and get super juiced up and then they grab three sodium by the neck and throw them out of the castle. Now the lords of potassium they don't want to live shoulder to shoulder and squalor like the peasants so only two potassium enter the castle for every three sodium that are thrown out of the castle. So there's always more of the nation of sodium outside the castle than there are people of potassium in the castle. Quick side note because this is such an important concept. The fact that these ATP pumps put three sodium out and two potassium in means there's always a larger amount of positively charged ions outside the cell than there are inside the cell and because there are relatively less positive charges in the cell that means that it is relatively more negative than outside the cell. And if something is negative, well that means it is polarized and something that is polarized can then be depolarized. Meaning we allow all of those parts. positively charged ions that are concentrated outside the cell to follow their natural concentration gradient and flow back into the cell. The negative charge in the cell is called a transmembrane potential. And when we depolarize it or allow all of our charges to kind of go back to an equilibrium, this is the basis of how our cells talk to each other. A depolarizing heart cell will tell the heart cell next to it to depolarize, or a depolarizing neuron will tell the neuron after it a specific message. Without setting up these different concentration of positively charged ions in and outside the cell, we're not able to depolarize in response to say stimulus. And being able to adapt or change in response to stimulus from your environment is incredibly important for everything, from monitoring your blood glucose to, say, keeping your blood pressure in a normal range. Okay, back to the story. So the very large nation of sodium has been expelled to the outer forests that surround the castle. And now the people of potassium are ruling inside the castle. Now as the new rulers, they don't want the lords of calcium hanging out with them. So they begin jailing them in the sarcoplasmic reticulagial. It's called a sarcoplasmic reticulum. It's basically just a big intracellular vat of calcium. Seeing the other lords of calcium being jailed, some of the calcium managed to flee outside and live with the nation of sodium, crowded together in the forests surrounding the castle. All of them eagerly hoping to get back into the castle. And this is where our story sort of begins. We have potassium ruling inside with calcium locked up in the sarcoplasmic reticulagial. We have the vast and large nation of sodium living in the forests surrounding the castle with some of the lords of calcium. Now the lords of calcium want to free their incarcerated people, but they don't have the numbers. However, the nation of sodium could easily overwhelm the castle gates, but they can't open up the locks to the sarcoplasmic reticulagial. They're too complex. Only the lords of calcium actually know how to open those gates. So an alliance is made. The nation of sodium with their vast numbers agrees to storm the gates and fight off the people of potassium. Once inside, they agree to open up the back door gates to allow the lords of calcium to sneak in and free their incarcerated people. So a plan is made. But remember, there's billions of castles. They need to not just conquer one, but all two billion in succession. So after they conquer the first castle and release the people of calcium from their jail, they'll raise a flag of victory, which will be the signal to tell the people of sodium to leave that castle and begin attacking the others around it. Sort of how depolarizing a heart cell is the signal to tell the cells next to it to begin depolarizing. So our story begins and the phases of the attack roll out like the four phases of the cardiac action potential. It starts with phase zero. The nation of sodium charges the castle and plays their drums of ore. Then phase one begins the nights of potassium who are comfortably living in the castle begin fleeing as sodium charges into the cell and you can hear their distressed sirens playing in the background. As potassium flees phase two begins sodium rushes to the doors and opens the gates for calcium to come in open the gate. And calcium rushes to the jail cell, the circle plasma reticulum, and breaks open the doors. This is calcium dependent calcium release. Now that calcium is free, it charges to the flag and raises it in triumphant victory. You can think of them pulling that flag as the pulling of the muscle fibers in the heart. So each castle that's conquered and raises its flag is a single heart cell squeezing. And this story plays out until every single castle is conquered. Meaning each castle or each cardiac cell squeezes so we can eject blood from the ventricle. And thus we get a full heartbeat once all the castles are conquered. But if this were the end of the story, you would never have another heartbeat. The whole process must happen again. Potassium coming back into the cell and ousting sodium. And then again sodium and calcium enter the cell and out potassium and continuing over and over for each heartbeat that you have. You could say the battle of these great nations is the driving force of the universe around it. So how do things reset? Well this is phase 3 of the depolarization cycle. As sodium and calcium are in the cell, potassium fleed the castle and it regrouped. It recharged. And after it's recharged, it simply returns with its well-paid ATP mercenaries that kick sodium out and allow potassium to live in the cell and jail the people of calcium. And thus the cycle restarts. Sodium enters the castle again. Potassium runs in fear. Calcium enters and frees its brothers. Open the gate! The flag is raised in victory. And potassium flees only to return with its mercenaries once again. And again sodium. Potassium. Calcium. Open the gate. And reset. And this happens over and over and over. A billion times in your lifetime. Cells depolarizing and repolarizing and synchronic. But when we add in the toxin that we talked about, it interferes with this whole cycle. You see, low paramide and other things that can lead to this arrhythmia torsas. They sort of sit in the doorways of the castle and prevent potassium from being able to flee when sodium arrives. If potassium can't leave as quickly, it can't recharge as quickly. So the whole process of resetting the heart cells begins to take longer. Open the gate! Open the gate! Open the gate! Open the gate! So now instead of all of the castles falling like dominoes, one after the other, some of the castles take too long to reset. And as we said, this creates conditions for arrhythmias to propagate. We won't go too much into the details since we covered some of the proposed mechanisms of arrhythmia generation and propagation in the first episode. And there's even more about things like early after depolarizations in the advanced mini-episode after this. But essentially, it causes things to get out of sync. And sometimes it can make it so that multiple depolarizing waves are occurring in the ventricle. And sometimes they collide in with each other. And if you have multiple areas trying to depolarize at the same time, they can sort of collide in with each other and create calamity. and as we mentioned, without the cardiac cells contracting in the right order, we don't get a nice unified ventricular squeeze so we're not able to eject blood. I don't think we need to go that much further into it since we covered a lot of this in the first episode. Now, one thing to note is that, unfortunately, as your ventricles stay in the repolarizing phase longer, you don't feel any different. But the longer you're in that state, the more likely you are to meet the right conditions that allow one of these arrhythmias to generate and propagate. Which is why users don't suspect anything until they wake up in an ambulance or a hospital. Alright, there you have it. I hope you enjoyed the saga of the siege of Castle Myocyte. I had some fun making it. I hope it was at least entertaining. If you want more, you can dive into the other many episodes where we talk a little bit more in depth about what some studies have suggested the actual propagation methods are of Torsatz. It's not the be-all-end-all, and remember, I'm not an electrophysiologist, but we rehash some interesting concepts. Remember, you can reach out to the show at [email protected]. Our Twitter is @labpoison. My Twitter is @eampoisonfarmd, and we have an Instagram Talks_Talk. And we appreciate you letting us know what you liked and what you didn't like. Anyways, I hope you can tune in for the next show with our special guest episode. I think it's going to be really entertaining. Till then, Talksau. Can you play us out? The information on this show is for educational purposes only, and should not be interpreted as medical advisor treatment recommendations. Please contact your doctor for any health questions. or call your local Poison Center at 1-800-222-1222 for Poison-related questions. The opinions expressed on this podcast do not represent those of our employers. This show is poorly written and shotally produced by Ryan Feldman. Subscribe for future episodes and don't forget to share with your nerdy friends. See you next time, goodbye.