Membrane Transport Mechanisms and Other Business

Hello All,

As I mentioned I will take your questions here and address them so all can find the answers to them.  There was not very many questions today, so either I did a fabulous job explaining the material (which I highly doubt) or maybe you have not yet gotten to this material, or maybe it really is review, or maybe you are nervous to contact me.  With that in mind, please remember three things: 1.  Don't let yourself get behind on material, there will be a lot of material covered and your time is VERY VALUABLE in medical school; 2.  This may feel like review, but it is at a different level than you have probably covered it in the past.  Therefore, work through some practice problems even if you feel like you know this stuff to know if you can answer questions similar on this material on the exam; and 3.  I promise I am approachable and available to answer your questions and NO QUESTION is stupid (chances are if you wondered it at least ONE other of you also wondered it so be brave and ask)!!!

Okay, so here ARE the questions that I received:  There was an initial question regarding logistics and then there are a few following questions about Membrane Transport.  Hopefully this posting is helpful.  If, however, it produces additional questions please do not hesitate to contact me either by posting a comment on the blog or by sending an email.

1.  This is regarding accessing your G-Drive Questions you mentioned today in lecture. Would you email detailed instructions on where to find them?

There are questions posted on the G-drive and you need to be accessing the network G-drive from on campus (not via a web-source).  In any folder for my lectures there will be additional folders titled 'study quiz' or 'thought questions'.  When on the network G-drive, copy the entire folder of either to your computer and then you can access the questions from that folder by pulling the 'quiz' into an open web-browser.

Alternatively, these same questions are available within the 'notes' section of the last two slides of every one of my lectures.

2. Are pores selective to what molecules can pass through? How do they regulate if they are selective?  If not then why are there different types of pores like aquaporins and connexin etc? 

Pores are SOMEWHAT selective, as in aquaporins are small enough that only water (and other molecules smaller than water) can move through them.  Connexin, or gap junctions, on the other hand are not very selective.  They allow for charged ions (virtually all charged ions) to move from one cell into another.  Pores, however, are not as selective to what they allow to move as channels and transporters where a signal needs to create them to open and for a transporter the actual molecule causes the transporter to transport the molecules.

3. I had a question on slide 17 of todays lecture. It says that the opening and closing of ion channels can be regulated by "Mechanical Forces".

What are these mechanical forces?

Great question.  Mechanical forces are physically (mechanically) pushing on the membrane causing an actual physical change in the membrane that causes the channel to open/close.  For example, your touch receptors on your fingers are mechanically gated and pressure on your skin causes them to open creating a change that ultimately results in your 'feeling' what you are touching.

4. I had a question regarding secondary active transport.  More specifically in slide 31.  I know that secondary active transport requires the energy one of substance in order to move another substance, in the example given Na is moving down the gradient which drives the transport of another molecule against its gradient.  My question is, is the Na moving down the gradient enough of a driving force to move the other molecule against its gradient without ATP/GTP? I got a little confused because in the notes of slide 26 it says that it needs ATP to establish a gradient with one of the substances.

Remember that the gradient that is being used (Na+ gradient for example) was created and is being maintained by a primary active transporter and the energy from ATP/GTP (typically Na/K ATPase for example).  Therefore, indirectly the secondary active transporter is utilizing the energy source and without it, the secondary active transporter could not continue to function. 

 

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 quiz – if 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!

Cardiac Muscles

Hello All,

I have placed two files on the G-drive (or they will be transferred within a day or two) that are the animations for the slow-response and fast-response action potentials for the heart.  They are HTML files, so please open them within a web browser and they should play.

Here are some questions regarding Cardiac Muscles that I have gotten from you.  Same as previously, I have grouped 'like' questions together and provided a single answer.  Questions are in blue, answers in red.  As always, if there are additional questions you have please feel free to comment on this posting or to send them to me individually!

1.  When you have fast-response AP, the last step, phase 4, resting membrane potential is achieved when you have the inward rectifier channels stay open and allow potassium to leave? I looked up what recitifier channels do and it states how they allow positive charges to move inward or into the cells. This make sense grafically, but in the elcture it says potasssium will efflux. I am a bit confused about what exactly is going on the phase 4.

I have a question regarding the fast-response ventricular/atrial muscle AP. During phase 4, if the the inward rectifier K+ channels are open, doesn't that mean that the K+ are coming in?  Please, correct me if I am wrong, because on the slide it says Efflux. But it makes more sense to me that it should be an influx since the current is inward and that it is maintaining the membrane potential. If K+ is moving out, shouldn't it make the cell more negative and thus hyperpolarize rather than depolarize?

As I mentioned in class, the names of these channels seem quite confusing and you would think an inward rectifier channel would be moving ions into the cell.  In the case of the K+ channels, however, K+ is STILL moving down its electrochemical gradient OUT OF the cell thereby repolarizing the membrane potential.  Therefore, the efflux that is stated in the notes and on the slides IS correct.  These channels are named after activities that they perform in experimental situations and are therefore confusing medically.  As I also mentioned in class, your current understanding of the K+ channels being responsible for repolarization and maintaining the resting membrane potential is STILL correct! 

2.  From the lecture slide, it stated that the Na/Ca exchanger takes in Ca and put out Na.  But I thought it is the other way around?

I am unsure where you have seen that.  On slide 24 it has the arrow for Ca2+ moving out of the cell (against its concentration gradient) and Na+ to be moving into the cell (with its concentration gradient), thereby working as a secondary active transporter.

3.  Does the AP from the slow response and the fast response start at the same time?  

They both start at when the membrane hits threshold, if that is what you are asking, but is that at the exact same moment in time?  No.  Remember that in every system, the neurons, skeletal muscles, and the heart muscle cells, that the action potential is the electrical current that travels.  In the heart, that electrical current is initiated at the pacemaking cells (typically the SA nodal cells) and propagates/travels from there to neighboring cells through gap junctions.  Therefore, the depolarization is spread to the next cell which causes it to reach threshold and the action potential to fire.


4.  For excitation-contraction coupling, is it only the cardiac muscle in the myocardium contracting?

Yes.  As Dr. Yin and Dr. Moore have both mentioned, the conducting cells do not have very much of the contractile proteins contained within their cell membrane.  You need actin and myosin in order for contraction to occur, and it is the myocardium that contains the cardiac muscle cells that contain those contractile proteins that, therefore, allow for contraction to occur.

5.  Is it correct to say that for the same afterload, with increasing preload will result in larger/higher shortening velocity (Vmax)?

Yes, that is certainly another way of interpreting that relationship!

6.  So for the heart, is increasing EDV the same as saying increased in preload?  If this is the case then, increasing EDV (increasing preload) will allow the ventricle to overcome the afterload a lot quicker?

Increasing the EDV is indeed the same as increasing the preload.  Increasing the EDV would, therefore, allow the ventricle to contract against a given afterload quicker (similar to what you stated above).  However, it does not allow the ventricle to overcome a greater afterload any quicker, but simply allows the ventricle to produce enough tension to contract against a greater afterload. 

7. How are Slow L type Ca Channels able to open to produce the plateau phase in the fast response Action Potential (since wouldn’t Ca2+’s Nernst potential approximately equal the membrane potential at that stage in the action potential)?

L-type Ca2+ channels are a voltage-gated Ca2+ channel that are initiated to open around the threshold value (same as the voltage-gated Na+ channels and voltage-gated K+ channels that we studied in the neuronal action potentials).  They are slower to open, however, and take awhile to open.  By the time they open the Na+ channels have already opened and inactivated and one type of K+ channel has already opened causing the 'notch phase' of the cardiac muscle action potential.  The equilibrium potential for Ca2+, however, is typically VERY positive (around +100 mV) and at that point in the AP the membrane potential, due to the movement of Na+ into the cell and then some K+ out of the cell, is positive, but not as positive as the equilibrium potential for Ca2+.  Therefore, the electrochemical driving force for Ca2+ at that point is still for Ca2+ to come into the cell.  So, when the L-type Ca2+ channels open, Ca2+ influxes, counteracting the efflux of K+ and that causes the plateau phase.

8. I would like to clarify: are dihydropyridine receptors a type of L-type Ca channel or are they completely interchangable terms? Or am I completely mistaken and they are not related? 

I just had a quick question regarding the dihydropyridine receptor. Is this receptor the actual L-type Calcium or T-type Calcium channel or one of the two or is it a separate entity all by itself?  

L-type Ca2+ channel and dihydropyridine receptors are completely interchangable terms.  There are two different types of Ca2+ channels in the heart that we have discussed, the L-type Ca2+ channel and the T-type Ca2+ channel.  The DHP receptor is another name for the L-type Ca2+ channel and is the SAME CHANNEL as the L-type Ca2+ channel.  Therefore, it would be accurate to alternatively say that there is the T-type Ca2+ channel (present in those cardiac cells that have automaticity), and there is the L-type Ca2+ channel otherwise known as the DHP Receptor that is present in all cardiac cells of the heart.