Monday, May 13, 2013

Membrane Transport Mechanisms

Hello All,

As I mentioned within lecture, I like to utilize this blog to clear up any confusions you may have regarding my lectures and to discuss any relevant or current topics surrounding this subject.  I received a few questions from the membrane transport mechanisms lecture and they are answered below.  If you wrote me an email with a question, it will be answered below.  Questions are in bold and answers given in blue.  If you have any follow-up questions please feel free to leave a 'comment' or write me an email and I will be happy to help you further!

1.  I was studying your lecture, and I am a little confused about the small red stars that you have below pores & channels as well as vesicular transport.  If I understood correctly, you mentioned that those stars mean that those mechanisms never reach maximal flux, and that they don't saturate.  Why doesn't simple diffusion also have a small red star?  If molecules are simply moving through the membrane, I do not understand why or how they would have a maximal flux. 

 I apologize, it may not have been clear what the small red 'stars' meant on that slide.  Now, the big red star indicates that I believe that figure to be a 'target figure', meaning that I believe that you can explain most all of what I was conveying in the lecture n that single figure.   

 The small red 'stars' are to notify to you that, although those mechanisms (channels/pores and vesicular transport respectively) are categorized how I documented them, they could be categorized differently under biochemical or cell biology definitions.  For example, the movement of molecules through pores and channels is classified as diffusion under the physiological definition because under the concentration differences that occur physiologically the movement of molecules through pores or channels never reaches a maximal flux (see slide 21 for a graphical representation of this).  As you increase the concentration difference, within physiological ranges, flux through pores or channels will increase continuously never reaching a maximal flux.

Vesicular transport, in contrast, has a small red 'star' because it falls into the 'active movement' category, but is not as simple as the hydrolysis of ATP, but is a more complete set of steps to cause either endocytosis or exocytosis.

2.  I was looking at the slides, and it seems that sodium is high outside the cell, but to move down it's concentration gradient into the cell where it's low it requires ATP. Is this because it has a charge ?

The movement of Na+ will always require some type of a protein as a charged molecule cannot simply move through the membrane without a pathway.  Now, there are a variety of pathways that the Na+ can take.  If Na+ moves through a channel (voltage-gated, ligand-gated, or mechanically-gated), it will move down its concentration gradient and not require ATP to do so (ie. the driving force will be passive diffusion).  If Na+ is moving through a secondary-active transporter as the molecule that is moving down its concentration gradient (remember, it is the most common + to utilize for secondary active transport), the movement of the Na+ is actually passive, but it is allowing for the movement of another molecule in an active-movement direction against its concentration gradient (example:  Na+/glucose co-transporter moves Na+ down its concentration gradient and the energy from that move allows glucose to move against its concentration gradient).  The gradient of Na+ that allows for it to move down its concentration gradient in each of the above examples, however, is maintained by a primary active transporter, typically the Na/K ATPase (pump) which directly utilizes ATP to move Na+ back against its concentration gradient to the extracellular side of the membrane.

3.  Regarding secondary active transport, are both steps uphill?  or Is primary creates the uphill energy difference, so that the secondary could use the energy to bring something downhill?  or does the secondary one use the energy to bring something UPhill, against its gradient?  The oval/star example illustrates both are uphill and against their gradient, but in one of your definitions for secondary, it says the secondary part is downhill.  So, just wanted some clarification on that. 

In secondary active transport, the primary creates the uphill energy (the movement of the ovals alone on slide 27) and the secondary active transport utilizes that energy to move something downhill (the ovals) and another molecule uphill (the stars).  Therefore, secondary active transport ALWAYS moves at least two molecules, one which moves downhill and one which moves uphill.  These can be in the same direction (co-transport) or in opposite directions (counter-transport) and the downhill gradient is ALWAYS maintained by a primary active transport of some type. 

4.  I am currently reviewing the lecture slides from "Membrane Transport Mechanisms" and i have a question regarding primary and secondary active transport. I just want to confirm that primary transport derives energy directly from ATP, while in secondary active transport, the energy is derived indirectly from ATP? Is this correct?

If asked whether secondary active transport requires ATP, would you say yes? I know it relies on ATP from primary active transport to establish a reversed gradient, ie not directly required, but if specifically asked, what would you say?

Yes, primary active transport directly derives energy from ATP while secondary active transport indirectly derives energy from ATP.  Now, what would I say about 'does secondary active transport require ATP?', I would say yes.  However, you need to remember any context that a question of that sort is given.  In my written exam questions it will be clear and I will indicate 'directly OR indirectly' if I mean both primary active and secondary active transport mechanisms.  However, in your future you may have this type of question not written by yours-truly...therefore, remember that you need to ALWAYS pick the BEST ANSWER CHOICE.  So, look at your contextual clues and if secondary active transport is truly the best answer choice, even though it is an indirect use of ATP, that may be the answer that should be best chosen.  

5.  For the Fick's equations, what is the formula for P? Is it P= DB/w? since in the 2nd equation we are getting rid of DB and w and using P and P takes thickness into account along w solubility into membrane and diffusion?

For our purposes now yes.  However, mathamatically speaking the 'permeability coefficient' actually takes into account additional information such as molecule size, fluid density, pathway for movement, etc.  However, remember that will be a constant given to us to utilize this equation.  You need to know that there IS a way to calculate the flux of a molecule and how it would change given the different mechanisms of movement across a plasma membrane.

Thursday, May 2, 2013

Welcome May 2013 Class

Welcome everyone to Ross University School of Medicine!  First semester is tough, but hopefully this blog will help you begin to put the pieces of the human body together and understand physiology.  After each lecture I will be posting here to include a list of the questions you have asked via email pertaining to the previous lecture and my responses.  The goal of this is to provide a common-location for you to go to with your physiology questions to obtain answers.  Please feel free to comment on the post and ask more questions.  If you have answers to previous questions, please additionally feel free to provide answers.  I hope that this can become a place for each of us to help each other learn physiology and all else that first-semester medicine proves difficult! 

Tips and Resources to Study Physiology:

According to The Free Dictionary (http://www.thefreedictionary.com), physiology is:
1. The biological study of the functions of living organisms and their parts.
2. All the functions of a living organism or any of its parts.

For our purposes at Ross University School of Medicine (RUSM), it is essentially the study of HOW the human body works.  This subject is quite difficult to memorize as it is constantly changing under a variety of conditions.  A conceptual understanding of physiology is, therefore, a much better approach to learning the subject.  I wish to provide you with a few helpful hints to studying physiology and the resources that are available for you here at RUSM.

Hints:
1.  Do not try to memorize physiological concepts.  They are built upon an understanding of the concepts and if you begin to look at them as such you will begin to understand the information and it will give you much less to remember. 
2.  Build all additional information you learn upon that which you already know.  Ask questions when being exposed to the information initially regarding where it will appear again and why it will be important (example: Membrane Transport Mechanisms).  Then when you see something again (example: Membrane Potentials utilize voltage-gated ion channels learned in Membrane Transport Mechanisms) build upon what you have already learned.  This, again, will cut down on what you need to remember.
3.  ASK questions.  Ask questions to yourself, your classmates, and your instructors to fully understand what is being presented to you.  If you are a person who learns a lot better if the information is clinical, challenge yourself and those who are helping in your education to help you understand WHY this basic science is important clinically.  This is professional education, you are being trained to be a doctor and ultimately this is YOUR education.  The work you put into it will reflect what you get out of your own education.  Materials and information will not simply be fed to you, so ask lots of questions to understand fully all of the materials that are being presented.

Resources you can utilize at RUSM:
1. Supplemental readings:  Each Physiology lecture will contain learning objectives and supplemental readings that will help you understand the information being presented.  Feel free to explore those readings.  If you are looking for a particular textbook, first check the library and then feel free to come see me to borrow my copy.
2.  Supplemental AV materials:  There is A LOT of information that will be presented in a short amount of time.  Utilizing 'cliff notes' or 'short cuts' to understand the information you are presented with will help you save time.  I have included youtube links that I think may be helpful within my lecture notes.  These are videos that I think are helpful.  They are certainly not the only videos available and I would love feedback you may have regarding the video links you like and do not like, but consider it a place to start to peek your understanding of the given topic.
3.  This blog:  As I stated above, I will post here after EVERY lecture all of the questions that I have received from you thus-far and my 'answers' to those questions.  Please feel free to utilize this as a discussion-board to continue the discussion to clear up anything that remains unclear.  Just post within the ‘comments’ section below (click on 'no comments' to bring up the ability to post a comment) any follow-up questions you may have and we can communicate with each other in that manor or always feel free to email me directly
4.  Articulate:  Articulate is program that allows you to take quizzes (both the thought problems and study quizzes are presented in this format, see info below).  They are available on the G-drive.  Regarding these quizzes the following are the 'directions':  
In the past, students have experienced problems when they try to run the Articulate quizzes from the “Students G-drive Online” connection, so please ONLY use the “Ross Net Drive [G drive]” available on campus.  In actuality, you do not need to run this quiz file from the G drive at all, and I recommend that you copy the entire folder onto your desktop or a USB drive and then run the quiz from any common browser (IE, Chrome, Firefox & Safari).  Note:  If you copy the folder off the G drive, be sure to copy the entire folder and not just the quizif you don’t have the contents of the entire folder (some application files are hidden) the quiz will not run.  Please email me if you experience any difficulties.  
In essence, go to the folder on the G-drive for the lecture (example: G:\Semester 1\Block 1. Fundamentals 1\Fundamentals.part 1\Membrane Transport Mechanisms Dr. Johannessen(PHYSIO)) and copy the folder within for either the thought questions or practice question onto your desktop or a USB drive (again, copy the ENTIRE folder as there are contents in the folder unseen that MUST BE present to operate the quiz), then open the quiz within a web browser by dragging the quiz file to an open web browser on your computer and the quiz itself should open automatically.  Either of the visible files within the folder should work within a web browser in this manner.  This needs to be taken from the G-drive ON CAMPUS (not the ‘online’ G-drive, but the actual drive on campus). You can do this on your personal computer while on campus or from a public campus computer. 
5.  Thought problems and Study Quizzes:  Practice questions are aimed to help you determine your understanding of the material presented.  Some of the practice questions given to you will be more difficult than those you will find on exams some will be less difficult.  These questions are always within the notes-section of the last two slides of each Powerpoint for my lectures and they are also available on the G-drive in the Articulate format (the exact same questions are therefore presented to you in 2 ways).  I encourage you to utilize Articulate if possible as they contain additional feedback that is not contained within the Powerpoint version.
6.  Center for Teaching and Learning:  The Center for Teaching and Learning (CTL) at RUSM is dedicated to your academic success.  Faculty within that department focus SOLELY on your success and are there to help you.  Cognitive Skills MCQ sessions allow for discussion amongst students with the guidance of a facilitator (I myself work as a facilitator there).  Additionally, the CTL offers one-on-one meetings, study-skills workshops, and any additional help that you and they can identify together that you may need.
7.  Hands-on experiences:  We do not have an extensive Physiology lab at RUSM, but some topics are better understood within that environment.  Therefore, I have access to a few computer-based laboratory exercises and would be happy to work through those with you as you see a need.
8.  Your Classmates:  There are almost 300 of you in your class and only about 50-75 faculty members who will be lecturing to you during this semester.  Therefore, your best resources are each other.  Please talk to each other and get to know each other.  Each of you came to RUSM with a variety of experiences and knowledge; therefore harvest each other’s knowledge to help you in your current learning.  You are all future colleagues and working with each other to all learn the material will only help you.

Hopefully these hints and resources will prove helpful.  This is your education and your future.  You are here at RUSM to train to be a professional, a medical professional.  It is our job as your educators to help you on that pathway and to provide guidance, but ultimately the hard work will need to be completed by you.  GOOD LUCK!

Wednesday, March 13, 2013

Cardiac Muscles

Hello All,

There were not a lot of question, but a few.  Since that was my last lecture for you this semester, I also wanted to wish you all luck in your studies for the remainder of the semester!

Here's some confusing points on cardiac muscle:



1. I just wanted to clarify one thing, you said that the heart solely relies on oxidative phosphorylation for energy.  This is under normal conditions, but I think we learned from Dr. Smolanhoff  that under starvation circumstances it can get it's energy from glycolysis too?

As I indicated in class that there are back-up energy sources (there certainly need to be), but that under normal physiological conditions the heart needs to have a significant amount of oxidative phosphorylation and a constant source of ATP.

2. I want to make sure I understand the last slide of "Cardiac Muscle" lecture: Force vs Velocity Relationship.  

Here is my take:

"I think what this graph is trying to say is that the stronger the pushing out of the blood, the lower the afterload.  So the top of the chart (directly on the Y-axis) means there was a huge pumping burst and it leaves just a little bit of blood left into the heart (afterload).

Correct or way off?


Afterload is the pressure within the cardiovascular system that the heart needs to pump blood against.  It is the equivalent of the force that the muscle fibers need to produce in order to move an object.  Just as in skeletal muscles, an increase in force needed, a decrease in shortening velocity.  However, the interesting point is that an increase in preload allows the heart to pump against a greater afterload.  An increase in preload causes stretching of the muscle fibers, thereby increasing the maximum isometric tension, thereby allowing for the cardiac muscle fibers to produce more tension.


3.a.I have a out of the box question about the permeability graphs for the fast and slow response mechanisms. First question in regard to the slow response. Both the T and L type channels open but at different intervals in time. Is this mostly due to the thresholds that are required to open them? Also what is the significance of the spike in Ca+ permeability with the T-type? Does it have to do with decreasing permeability of K+ that is occurring at the same time?

In general, voltage-gated ion channels are opened by a change in voltage.  The voltage that causes them to open, however, varies.  The voltage that opens the If channels is hyperpolarized.  That allows for Na+ to flow into the cell, thereby depolarizing the membrane to a voltage that causes the T-type Ca2+ channels to open.  Influx of Ca2+ through the T-type Ca2+ channel then causes more depolarization of the membrane to a voltage that causes the L-type Ca2+ channels to open leading to the greater depolarization of the membrane.  There really is no significance in the spike in Ca2+ permeability through the T-type Ca2+ channels other than the fact that it causes the depolarization that opens the L-type Ca2+ channels.

3.b. Second question is the change in permeability of K+ in the fast response. It changes when the Ca+ channel is opened during the plateau phase. (it dips down then raises again) Is the change in permeability more due to the affect on the channels or the change in membrane potential because of the change in Ca permeability.

As I indicated in class, there are a variety of K+ channels in the cardiac muscles.  The K+ permeability indicates the total permeability for K+ in these cells through all of these channels.  Therefore, the permeability changes when different channels open and close not due to the changes in Ca2+ permeability.  The changes in Ca2+ permeability change the membrane potential and that can cause different K+ channels to open or close.


4. I'm really struggling with the question below because I know that an influx of Na+ causes depolarization:  Also, are Purkinje fibers and bundle of his considered slow or fast response? Where do they come in to play in all of this?
12.  Which of the following is the result of an inward Na+ current?
            A.  Upstroke of the action potential in the sinoatrial (SA) node
            B.  Upstroke of the action potential in Purkinje fibers
            C.  Plateau of the action potential in ventricular muscle
            D.  Repolarization of the action potential in ventricular muscle
            E.  Repolarization of the action potential in the SA node

Please refer to slide 23 for further information.  The Purkinje fibers are cells of the conducting pathway of the heart and have If conductances, T-type and L-type Ca2+ channels, voltage-gated Na+ channels and K+ channels.  Therefore, they have an action potential that is both slow and fast response.  They have the ability to have phase 4 depolarization and initiate their own action potential, but also have a fast depolarization due to the opening of voltage-gated Na+ channels and a delayed repolarization phase.

Therefore, with respect to that question, SA nodal cells do not have voltage-gated Na+ channels and, therefore, the influx of Na+ will not cause the upstroke of their action potential. Purkinje fibers, however,  do have a quick depolarization caused by the inward current of Na+.