FUNdamentals

9.11.08

11-12

Bevensee

….recording starts late….

Slide 1 (contact information)

Outline Slide (not in the PowerPoint, but she showed it in the presentation)

  • This lecture will be more straightforward, but the next 3 lectures might pose some issues for some people. There are some concepts that are little difficult to grasp.
  • If you do understand the concepts I present, it’s going to make some of the rest of the physiology lectures a lot easier to understand. It is important to really get a good grasp of the information and the concepts I am going to present.
  • I am going to talk to you about biological membranes, not the structure, but the functional roles of biological membranes and the principles of solute and water movement across a biological membrane.
  • We are going to talk about the simple concepts of diffusion and osmosis as they relate to transport across membranes. Also, the principles of ion movements; when you have a charged molecule – how that actually moves across the membrane and what proteins are involved in the movement of ionically charged molecules.
  • We are going to talk about membrane transport in a lot of detail; we are going to talk about how proteins and solutes can move across the membranes, both through the membrane and though specialized membrane functions.
  • What I am going to do is talk about various carrier proteins and ion channels that are involved in the movement of ions and solutes across the membranes.
  • In the last lecture, I will incorporate the knowledge you get from the next few slides, next few lectures rather, and use the nerve action potential and epithelial transport to illustrate how you can incorporate the transport proteins used in movement of solute into cell functions.
  • I am going to provide you with a handout, but yesterday a very nice virus decided to attack my computer which is now in the hospital. It’s not available yet, but I will have it available to you but you don’t need it for the information this morning. What I will do on each of the slides I present is I will have a little blurb next to them with the salient points on each of those slides.
  • Again, if there is any of that information that is not clear or you want more information, just feel free to contact me.
  • I am also going to give you a problem set. In the past when I had given these lectures, we have a review session in which I have covered problem sets that involved diffusion and osmosis and also the generation of membrane potentials. This is not mandatory, but I’d advise you to have a stab at the questions. What I will do is present you with a problem set, but I will also give you an answer sheet. It’s probably worth getting together in small groups and trying to go through the questions together, and then if you have any problems with them, I can get together with your small groups or with you individually to go through, especially with the part where you talk about the generation of membrane potentials and equilibrium potentials. This is going to come up time and time again in the physiology course and quite honestly, if you have a good grasp of that information, it’s going to make things when you talk about different cell functions that involve changing membrane potentials a lot easier to understand.

Slide 2: The Cell: The basic unit of life

  • This morning’s lecture is going to cover some of the cell’s functions, membrane functions that are involved in transport across membranes. Just to introduce the slide– you know what a cell looks like.
  • You have had a lot of the information in various forms, but what I am going to try to do today is build upon the information that you have had before and add to it, and introduce the concepts and topics that I am going to be presenting to you.
  • If I talk too fast, will someone raise their hand…designate a hand waver.
  • The cell is the basic unit of life. It is the way through which we obtain food and oxygen. The cell membranes in cells are capable of obtaining oxygen, which is used to generate energy in the cell. Cells are also involved in eliminating waste substances, they are involved in protein synthesis, responding to environmental changes and also controlling the exchange of substances. They have many many more functions.

Slide 3: image of cells

  • The cell membranes come in various forms. Dr. Whikehart has told you a lot about the structural components of cell membranes.
  • As well as plasma membrane, which is the outside of the cell, there are also various membranes in the cell and various structures in the cell that are involved in the overall function of a cell.
  • The proteins and lipids that constitute cell membranes are varied depending of the cell type, where you find it in the body, and varied upon the role that they play within the cell itself.

Slide 4: image

  • Within the body, there are basically 2 overall compartments – the extracellular fluid compartment and the intracellular fluid compartment.
  • I am going to introduce the membranes that are involved in maintaining the various compositions of the intracellular and extracellular fluids.
  • The extracellular fluid compartment is composed of the interstitial fluid and the plasma fluid and also a specialized smaller volume of fluid – the transcellular fluid.
  • The transcellular fluid is found in synovial fluid or in the cerebral spinal fluid which is the fluid that bathes the brain.
  • Fluid movement and solute movement across the cell membranes of each of these various compartments is controlled very tightly by various proteins that you will find in cell membranes.
  • The intracellular fluid compartment composes 40% of the total body weight. This is the largest fluid compartment of the body.
  • Within the intracellular and extracellular fluid, the actual composition of the fluid contained in those 2 compartments is highly regulated and it varies from one type of cell or one type of fluid compartment to another. Again, the protein components involved in generating those gradients and differences are going to be the topic, especially of the 2 lectures tomorrow.

Slide 5: Solute compositions of key fluid components

  • So the solute composition within each of the fluid compartments, like I said, is very different.
  • For example, in the extracellular fluid, there is a high concentration of Na verse a high concentration K in the intracellular fluid.
  • Anyone had this info before…arts verse science background. You can go to sleep; this is all review for you.
  • The K concentration on the extracellular fluid is much lower than the intracellular fluid. Do you know why? (she doesn’t answer the question)
  • It is also because many cellular processes within the cell require a high concentration of K, as well as a generation of that gradient due to the activity of the Na/K pump. Will get more of that tomorrow.
  • Within the cell, we maintain a very low concentration of Ca verse a relatively much higher concentration of Ca on the extracellular side. This is very important point because Ca is involved in many regulatory processes within the cell and also involved in cell contractions. As you go through your physiology course, you will find out why that concentration must be maintained at a lower level verses a higher concentration on the outside. We are not going to go into the details of that, but that is very important point to remember, that concentration of Ca inside the cell is low.
  • Listed here- you don’t need to memorize these exact concentrations, but various cells have slightly different concentrations and you will see various cell models that are presented when people will give an arbitrary number that is approximately what you would find in a physiological fluid solution.
  • One of the important points to know is that even though there are a variety of osmolitcally active solutes within the cell, the osmolality is constant from the extracellular fluid to the intracellular fluid.
  • We are going to talk about osmosis and the movement of solutes tomorrow, but this is important to note that the osmolality is constant. If it wasn’t constant, the cells would either shrink or swell depending on the principles that were involved in that process.
  • Another important thing to note is that cell proteins comprise 10-20% of the cell mass. Within the cell there is a higher concentration of proteins than in the extracellular side. We are going to talk about the importance of intracellular protein concentrations tomorrow when we talk about doning(?) equilibrium. For now remember that there is a higher concentration of solutes within the cell than outside the cell.
  • The various compositions within the intracellular and extracellular solutions are given by different SI units. What is shown here is milliequivalents – that is because you are looking at a charged molecule. Equivalents relate to the charge of the substance and molar here refers to the concentration of the osmotically active solute.
  • Here you have, for example, where proteins are charged. Again, you have a charged species, so you need to take the equivalent into consideration.

Slide 6: Cellular membranes

  • I will give some information about the exact definitions in the handouts I give you to reiterate the point that you will see millimoles verse moles. I will give you those definitions in the handout; it’s just in this case they are using milliequivalents.
  • The basic structure of cell membranes is shown here – it’s already been described to you, but just to reiterate the point that the cell membrane has an appearance like a railroad track. This is 2 cells abutting each other. This is not the lipid bilayer you have been talking about; this is 2 lipid bilayers where 2 cells are sitting next to each other.
  • The cell membranes, as you know, separate the cells from the outside world. Again, they also separate the intracellular compartments – the solution within those compartments verse the cytosol for example.
  • There are proteins contained in each one of those membranes that are specific to the role of that compartment.
  • They also provide a scaffolding mechanism for membrane proteins. Even though under a microscope the appearance of the membranes look very very similar and there are general functions that are common to all cell membranes.
  • The important point to take from this slide is that there is a diverse number of proteins that are found in different cell membranes and they are very specific for the role that each one of those membranes are required to undertake and also for the membranes that you find them in.

Slide 7: image of lipid bilayer

  • So again, this is to highlight the information that Dr. Whikehart told you – here is another diagram of a cell. What this shows is the lipid bilayer that forms the cell membrane.
  • Interspersed within that membrane are integral membrane proteins and peripheral proteins. You know that the integral membrane proteins will actually transverse the lipid bilayer; peripheral proteins kind of sit in the bilayer.
  • Within the lipids and proteins contained within the cell membrane, there are covalently attached sugar molecules. These are found on the extracellular surface of the cell membrane.
  • Within the intracellular aspect, we have a meshwork of protein subunits that we will talk about later. Again, this is just to illustrate that there are proteins contained within the lipid bilayer and those proteins are what I am going to be predominately talking about tomorrow.

Slide 9: Glycocalyx (she skips slide 8 and then goes back to it.)

  • So polysaccharide molecules that are attached to lipids and proteins within the cell membrane are there – they form the membrane glycocalyx – the cell coat.
  • Again, they are covalently attached to the lipids and the proteins of the cell membrane. Their sugar chains are added in the endoplasmic reticulum and are further modified in the Golgi.
  • What these carbohydrates do is they absorb water so they form a slimy coat that protects the cell from harsh environments. They protect it from chemical and mechanical damage.
  • There are also involved in cell-cell recognition, so they are the basis for the function of an organism in cells that are able to sort in the embryonic stage that varies in tissues and organs.
  • They are also involved in the immune system by the immune system being able to recognize a foreign cell in the body.

Slide 8: Membranes are selectively permeable

  • The proteins and the lipids that form the membrane generate a selectively permeable membrane.
  • Again, as you know, the lipids that form the membrane, predominately the phospholipids enable the lipid membrane to be permeable to certain substances.
  • For example, small hydrophobic molecules can freely transverse the cell membrane – they don’t need any extra help to get across. They can free diffuse across the cell membrane.
  • Also, small unchanged molecules such as ethanol and water can also transverse the cell membrane.
  • One thing to note here regarding water is that it can not only move across the membrane but there are also specialized proteins known as aquaporins that I will talk about later, that are also involved in the movement of water across the membrane.
  • Water can freely diffuse across the lipid bilayer, but there are also specialized proteins that enable water to. When you do the renal physiology course, the importance of aquaporins will be reiterated at that point.
  • When it comes to large uncharged polar molecules and or charged molecules, ions, the actually need a little bit of help to get across the membrane because of the functional characteristics of the lipid bilayer, they can’t move across the membrane on their own. We are going to about the proteins involved in getting those substances and solutes across the cell membrane.

Slide 10: Diagram

  • What I am going to talk about next, again we are looking at another diagrammatic representation of the cell membrane, is the proteins that are involved in the extracellular surface and the intracellular surface.

Slide 11: Cytoskeleton

  • First, the cytoskeleton. The cytoskeleton is (I believe Dr. Cotlin introduced the cytoskeleton to you) illustrated as string like fibers.
  • The role of the cytoskeleton is to provide stiffening and a support for the cell. Also, it provides anchorage for proteins in the cell itself or in the cell membrane.
  • It is also involved in the dynamics of cells. So cells that can crawl, that the change the configuration of the cytoskeletal proteins are involved in this movement of whole cells and reproductions.
  • There are 3 types of cytoskeletal fibers that you have been introduced to – microtubules, tublin, microfilaments, actin and intermediate filaments.

Slide 12: EM and micrograph images

  • This is a micrograph of microtubules within fibroblasts and this is another EM showing microtubules (don’t know how clear – my eyesight is not that great) and filaments.
  • Microtubules are composed of heterodimers –a type of protein known as alpha tublin and Beta tublin. Those heterodimers will assemble and dissemble at the ends of the microtubule tube, if you will.
  • Microtubules are involved with functions inside the cell and also in the structural basis of cell membranes.

Slide 13: Membrane-cytoskeleton attachments in the RBC

  • The proteins that can be associated with cytoskeleton can either be embedded in the cell membrane or they can be proteins inside the cell as you can see here. This is illustrated in this diagram here.
  • As well as structural elements, these microtubules are involved in moving proteins around the cell membrane.
  • Not quite sure what you got on the mosaic model of the cell membrane, but it used to be thought that cell membrane proteins were embedded within the membrane and just didn’t move.
  • I believe you have been introduced to the Fryin-Endel model (?) where you can actually see the movement of proteins. Some are freely able to diffuse around the membrane and some are actually involved in moving by the presence of microtubules and microfilaments as part of the cytoskeleton.
  • It just depends on the protein and its movement with the cytoskeleton whether it can freely swim around the membrane. Over the years, that cell model, the fluid mosaic model has been modified over and over again. The same premise for the model exists, but the fact that membrane proteins can move around freely has now been demonstrated experimentally and in micrograph type pictures, too.
  • She will be giving us a handout that will have the latest version of the slides that are being presented; She added a few little bits here and there; everything that she is going to present to us will be in the handout and we will have that by this afternoon(Thursday) if she can get to a computer to work.
  • If you print off on PowerPoint, you can print off where you have pictures and then notes. The exact notes that she has regarding each slide (not a verbose long list, just what she considers the main points will be listed in the notes portion things that she finds helpful will be listed so we do not have to read 10 text books to get a grasp on the material.)
  • In past years when she has given these out, the students have found them helpful. It is going to be the main points on the slides and she tries to highlight and bold the really important points that we need to remember.
  • Dr. Whikehart will be posting what she sends to him on WebCT. The problem set that she mentioned at the beginning of lecture will be passed on to Dr. Whikehart because she did not have the ability to upload her handout. He will have everything. If she makes any changes to any of her notes/handout by adding any necessary and extra information, she will sent out an updated version to Dr. Whikehart to upload.
  • She said we will have exactly what we need to know from her handouts/problems set/PowerPoint lectures so there is no need to be scribbling down anything.
  • This does not mean we should not come to lecture because there will be ARS questions.
  • The exact slides that were presented in class will be given us; we could not have them today due to her computer’s virus.

Slide 14: Structural Junctions