Appendix 1: Communication Principles Podcast Transcript
Hey everyone! This is Sydney, coming to you from the University of Guelph. Welcome to the first Human Physiology I Podcast. My partner Hanna and I started this podcast to give you guys another way to learn. Both Hanna and I learned the content for this course by having a partner or a group of people who were in the course that we were able to talk things through and bounce ideas off. So that’s why we’re here. We’re going to be doing the talking for you, talking through tricky concepts, addressing common problems and questions to help try to build your understanding of the course so that you can all be successful. So let’s get right into it then, starting with your first unit, communications principles.
Hi everyone, I’m Hanna and we’re gonna start by talking about membrane transport. So an important concept of this subunit is the electrochemical gradient. An electrochemical gradient is based off of both an electrical gradient and a concentration gradient. The electrical gradient will move ions across a membrane based on their charge. We can think about how positive potassium ions would move across a membrane if the other side of the membrane has a more negative charge so they’d be attracted to it. The electrochemical gradient is also made up of a concentration gradient, which moves substances from areas of higher to lower concentration.
We have found that a common problem that students have with this concept is just knowing the difference between the phrases “with the concentration gradient” versus “against the concentration gradient.” The phrase “with the concentration gradient” means that a substance is moving from areas of higher to lower concentration, which is how ions would normally move. The phrase “against the concentration gradient” means that an ion is moving from areas of lower to higher concentration which can’t be done passively, it cannot be done without energy.
Hanna: We also need to think about how substances are able to move across the plasma membrane. There are two methods of active transport, primary active transport and secondary active transport. Primary active transport uses ATP to move substances across the membrane “against” their concentration gradient, this creates an electrochemical gradient across the membrane.
An example of this primary transport is the sodium potassium pump, which you will see more of later on in the course. The sodium potassium pump is responsible for maintaining the electrochemical gradient by moving potassium ions into the cell and sodium ions out of the cell. Since they’re moving against their concentration gradients, energy is required, therefore it uses ATP.
The electrochemical gradient that is created by primary active transport, can drive movement of other substances across the plasma membrane, this is called secondary active transport. So because it’s being driven by primary active transport, secondary active transport actually doesn’t require any energy, or ATP. Hopefully that clarifies some concepts of membrane transport. Now we’re going to talk about the bioelectricity subunit, and think more about how and why ions move across membranes.
An important concept is resting membrane potential. The resting membrane potential in a typical neuron in our bodies is about (negative) -70mV. A common misconception is that since the membrane potential is “at rest” why is the cell keeping it a negative number, (minus) -70, and not at an equilibrium of 0mV?
That’s because the membrane is not equally permeable to all ions. There are a number of different protein, ligand-gated or voltage-gated channels, on the cell membrane, moving different ions and proteins into and out of the cell at all times. So there’s a different concentration of positive or negative ions inside and outside of the cell and it’s not at an equilibrium of 0mV across the plasma membrane. This movement has a lot to do with the ion equilibrium potentials, which we will talk about soon.
We’re going to just talk about some of the equations that were covered in class. I know some of the numbers can seem overwhelming so we’re going to break them down to why they’re significant. To calculate membrane potential in our bodies, we will use the Goldmann equation. This calculates membrane potential when a membrane is permeable to multiple ions, like in our body where potassium, sodium and chlorine ions are main contributors to membrane potential. The Nernst equation looks at one ion at a time, and calculates the equilibrium potential for that specific ion. So for example, Sodium ions have an equilibrium potential of (positive)+68mV. If the membrane potential is (minus)-20mV, you can think about which way the sodium ions would move.
So in this case, the positive sodium ions will move into the cell in an attempt to make the membrane potential more positive, since sodium ions want to reach their equilibrium potential of (positive) +68mV. A helpful tip is to remember that ions always want to move across the membrane in a direction that would make them reach their equilibrium potential.
But, before you try to figure any of that out make sure you think about relative permeability. So we’ll use calcium ions as an example of why. The relative permeability of calcium ions is 0, meaning even if Calcium (Ca++) wants to move to reach its equilibrium potential, because the membrane is impermeable to Calcium ions(Ca++), they can’t move. So if you look for that first, you can save yourself time trying to figure out how it’s going to move, because it won’t. Now that we’ve talked about ion movement, we’re going to discuss action potentials, which are a core concept of this course. Almost everything else you learn throughout this course will be based around this idea. So make sure you develop a strong understanding.
The first thing you need to remember is that an action potential is an all or nothing event. Which means the “size” of the action potential does not change, just the size of stimulus influences the frequency or pattern of multiple action potentials. For example if your nerves are responding to a stronger stimulus like feeling a slap on the back versus a pat on the back , this doesn’t mean there’s a “bigger” action potential from your nerves, the sensation would just be sent in a different and more frequent pattern for the slap versus the pat. So for example, the pattern of action potentials for a hard slap could be “boomboomboomboom” but a light pat could be sent as a slower “boom boom boom”
Okay so I’m going to talk through an Action Potential. Just know that through this if I say sodium or potassium channels, I’m talking about the voltage-gated ion channel. A cell membrane of a neuron in the human body starts at (minus)-70mV. That’s the resting membrane potential. Action Potentials are started by a stimulus, so something hitting you or feeling something, anything like that. That stimulus makes the membrane more positive and it will reach a threshold. So threshold isn’t necessarily a set number, it’s just a charge the membrane will reach that will start the Action Potential. At this threshold, voltage-gated sodium ion (Na++) channels open. If you’ll remember from earlier, ions move to reach their equilibrium potential which for sodium ions is (positive) +68mV. Since the membrane is still negative right now, at threshold, sodium ions (Na+) will want to move into the cell to make it more positive.
So this process of the cell becoming more positive is called “depolarization”. After about 1ms Sodium (Na+) channels become inactive and depolarization stops. This occurs around 0mV.
Remember the difference between these channels becoming inactive and closing. We’ll bring that up briefly when we discuss refractory periods.
Right so right now they are inactive but they will eventually close.
Next Potassium ions (K+) channels will open up and potassium ions (K+) will start to move out of the cells. So why is potassium (K+) moving out? Because their equilibrium potential is -90mV so it will move to make the membrane more negative. This process of the membrane becoming more negative is known as the repolarization period.
The cell will repolarize below the initial resting membrane potential, so below (minus)-70mV where it started out. When it’s more negative than that value, more negative than (minus)-70mV, this is known as hyperpolarization. K+ channels will then become inactive, eventually closing, and the membrane will return back up to resting membrane potential.
The sodium-potassium pump, is what brings the membrane potential from hyperpolarization back to resting membrane potential. A common question that students have is that if sodium is causing depolarization along the length of the cell membrane, what’s stopping the action potential from traveling backwards? Don’t forget that fast, voltage-gated sodium channels are inactive at the peak of the depolarization, during the absolute refractory period. When they are inactive, it means that they can’t open up again for a brief time. Because of this, depolarization won’t spread back towards previously opened channels. So the action potential moves forwards towards the end of the neuron and then to the next neuron. This is a classic example of cell asymmetry which allows the action potential to move forward and not backwards.
Refractory periods are a tough concept for many of us, I would say the key is knowing the difference between an inactive channel and a closed channel. So remember an inactive channel cannot be reopened from this state but a closed channel can. In the absolute refractory period, another AP can’t be generated even if you apply a stimulus because all the voltage gated sodium ion channels are either open or inactive, and therefore cannot be reopened.
Also remember during the relative refractory period, the sodium channels are closed, so it is possible to generate another AP, but you would need a bigger stimulus to do so. We also want to talk about the myelination of nerves, and give an interesting practical example of myelinated versus unmyelinated nerves to help us to remember the difference between them. We can think about demyelinating diseases, which are diseases in which there is damage to the myelin sheath of nerves. So if there is damage to the myelin sheath of myelinated nerves, action potentials will slow down while travelling along the nerve, which can cause neurological problems. The most common demyelinating disease that affects the central nervous system is multiple sclerosis, which can result in vision loss, muscle spasms, a loss of coordination and changes in sensation. For this course, remember that if a nerve is myelinated, an action potential will travel further and decay slower, and an action potential will travel slower and decay faster in an unmyelinated nerve.
Before we talk about synapses, let’s take a minute to think about local current. This is a concept I struggled with at first. So local current travels along a neuron so that a positive charge can be passed to a postsynaptic neuron. It starts with an action potential happening at some part of the cell membrane, in this case, it’s a neuron and it’s happening on the axon membrane. So we’re going to call this place where the action potential occurs on the axon membrane, that’s going to be section A. So the AP makes section A more positive.
Section A’s Neighbour, section B is more negative so the negative ions of section B are attracted to section A and will move to section A. So now in section B, there’s fewer negative ions, so section B is more positive. Section B’s neighbour is section C, an it’s more negative than section B so negative ions from C will move to its neighbour section B. This will continue down the axon through sections D, E, F, however many it takes, until another AP occurs, or the charge will reach the voltage gated calcium ion channels which will start a synapse. Which we’ll talk about right now.
Electrical synapses are the way signals are sent from one cell to another. There’s a space between these cells so there needs to be a way for a signal to be passed across this space. There’s 2 types of synapses: nerve to skeletal muscle synapse and there’s nerve to nerve synapses. We’ll start with Sydney talking about nerve to skeletal muscle synapses.
The synapse starts when local current reaches a voltage gated calcium ion channel on the presynaptic nerve. The channel opens and calcium (Ca++) fluxes in and promotes the vesicles containing neurotransmitters to fuse to the plasma membrane. So these vesicles fuse and then kind of open up and that opens the plasma membrane it’s attached to so neurotransmitters are able to exit through into the synaptic cleft. So that’s the space in between the two cells. From there, we want the neurotransmitter to bind to the ligand gated sodium ion channels and open them up. Note here that they’re sodium ion (Na+) channels, so it will be sodium ions entering into the post synaptic cleft, not the actual neurotransmitter. The neurotransmitter is just acting as the ligand or key to open the channels. As we know, sodium ions (Na+) will make the cell membrane more positive, local current will act to pass this signal down the membrane, opening sodium ion (Na+) channels on the axon, therefore continuing the AP in the postsynaptic nerve.
When we look at nerve to nerve synapses, there are signals called excitatory postsynaptic signals, which are called EPSPs, or inhibitory postsynaptic signals, which are IPSPs. The passing on of a signal to the next neuron depends on the sum of these EPSPs and IPSPs. EPSPs, the excitatory signals, are positive and IPSPs are negative. You need multiple EPSPs to reach threshold, and the EPSPs can come from multiple presynaptic neurons, or from one presynaptic neuron that sends multiple repeated signals. I like to think of EPSPs as small positive charges, and if you get enough at the next neuron, which is called the post synaptic neuron, you can hit threshold to make an action potential which means that the signal is moving forward to the next neuron. In contrast, if there are more IPSP signals, nothing will happen because you’re making the cell membrane of the next neuron more negative and taking it further from threshold. Remember, the two signals cancel each other out so you need more EPSPs than IPSPs to pass the excitatory signal along.
Now that we talked about synapses, go ahead and look at specifically Metabotropic Chemical Synapses. The only thing I’m going to really say about this is that the key thing to remember for these is that it’s not the neurotransmitter that is deciding what actions will happen in the postsynaptic cell. It’s the receptor that the neurotransmitter binds to and the associated G-protein.
One way to think about this concept is by thinking about the pharmaceutical implications. We can think about how medicines contain ligands to fit membrane receptors that will ultimately have an effect on your body. So instead of making a drug that will slow down your heart rate, we make a drug that will bind to receptors that are associated with G-proteins that will signal a pathway to slow down your heart rate. Another way we can think about this is with the example of “beta-blocker’ drugs. These drugs block beta receptors in the heart, which prevents receptors responsible for increasing HR from being binded to and activated by epinephrine. Instead of getting rid of epinephrine or making a new NT to act, we can use drugs to block receptors instead.
Now we’ll talk about what I found was the most complicated part of this course which was the actual action of the muscles, muscle contractions and the different calcium (Ca++) sources associated. The main source of calcium (Ca++) for muscle contractions is intracellular calcium (Ca++). This intracellular calcium that is also used for contractions is released from the sarcoplasmic reticulum, which is a kind of storage compartment found within cells. The calcium fluxes into the cell (extracellular calcium) and will open calcium ion (Ca++) channels on the sarcoplasmic reticulum. That means it’s ligand gated, since it’s extracellular calcium that is triggering the opening of these channels, and the intracellular calcium ion release.
In skeletal muscle, there is a different mechanism that releases intracellular calcium. It starts with an AP that travels down t-tubules of the muscles. When the charge of the membrane associated with the dhp receptor increases, dhp changes shape which causes it to pulls on ryr, and the calcium ion channel opens, and because this channel was initiated by the charge on the membrane associated with the dhp receptor, this is a voltage-gated channel which opens and releases intracellular calcium. Calcium then goes to find troponin which is the start of the mechanism for the actual contraction.
We’re gonna look at striated muscle contraction in cardiac and skeletal muscle. When thinking about actin and myosin, I like to keep in mind that Actin is always attracted to Myosin when it’s with inorganic phosphate, which we’re going to call it Pi for short. And Actin won’t stay with ATP. so remember those two parts. So when myosin is with Pi and ADP, Actin binds to them. This leaves actin, myosin, Pi, ADP together. When ADP and Pi leave, the force generating power stroke occurs, this is a conformational change in the myosin head. Then, ATP is going to join actin-myosin. Now that ATP is binded, Actin doesn’t wanna be there so it leaves. This leaves Myosin and ATP alone. ATP is cleaved by the myosin head and breaks into Pi and ADP. Okay that was a lot, so now I’m going to send it back over to Hanna to go over this again with the best, most unforgettable explanation of all this. And if you want to modify this story at all to suit your personal life experiences, and just make it easier for yourself to remember, go ahead. Alright, take it away Hanna.
I like to think about this whole process in relation to people and relationships. First I think of Pi-ADP as a couple who are always together, and are going to come and go together. Initially, myosin, is hanging out with their friends who are the couple, Pi and ADP. Actin shows up and binds to myosin, because actin has a crush on myosin so it sticks to it. Now, actin, myosin, Pi and ADP are are all hanging out together. Then the power couple, Pi and ADP, leave which is an action called the power stroke. Now that actin and myosin are alone, myosin’s friend, ATP, shows up and binds to myosin, so that actin, myosin and ATP are together. But, actin hates when myosin and ATP are together so actin leaves the room, leaving myosin and ATP alone together. Now, the final thing to remember that doesn’t really work with the people scenario, is that the myosin head cleaves ATP into ADP and Pi, which leaves us with our initial conformation of Myosin and the couple, Pi and ADP being together, and the cycle continues. The same relationship concepts work for remembering smooth muscle contraction, you just need to remember that Myosin is phosphorylated the whole time during the process. To remember these relationships, I found it fun when studying to put names of people you know, maybe couples or friends you know that would fit this narrative. Or if you can’t think of anyone you can use names that relate to the words, for example Myosin could be Mitch, Pi could be Peter, ADP could be Dana, ATP could be Tristan, and Actin could be Ashley. So that’s my weird way that my friends and I came up with to remember the process of striated and smooth muscle contraction when we were taking the course, so I hope it helps.
Okay that concludes our first Physiology I podcast for Communications: Principles. Hopefully that helped you guys understand some of the content and you’ll be able to apply the concepts we’ve explained to some application problems as you work throughout the course. Tune in again to our next podcast where we talk about the Central Nervous System.
