MCB Exam 2 Review Session Fall 2018

Nernst vs GHK

Nernst equation The membrane potential at which an ion will be in electrochemical equilibrium What is electrochemical equilibrium? Chemical driving force down concentration gradient is balanced by the electrical force in opposite direction No net flux of ion (but ions are still moving!) Don’t have to use energy to maintain the existing concentration gradient Important to know this is theoretical. Specific to a single ion. Does not take into account other ions or permeability of the channels. Example: One cell only permeable to K. K normally high intracellular and low extracellular. Concentration gradient (chemical force) would drive K out of cell. K leaving generates buildup of negative charge inside cell – electric force that would want to drive positive charges (e.g. K) back in (buildup of pos chage on outside membrane, neg charge inside membrane). Eventually reach an equilibrium where chemical force = electrical force and so there’s not net movement of K.

Goldman Hodgkin Katz Equation Takes whole system into account – Nernst equation for all permeable ions + relative permeability of those channels Describes steady state condition Multiple ions (e.g. Na, K, Cl) contribute to the membrane potential so final membrane potential usually not equal to any one ion’s Nernst potential If membrane potential is not equal to ion Nernst potential then that ion is not at equilibrium  net flux Balance of these fluxes (Na in, K and Cl out)  maintenance of the same charge separation across membrane  stable resting membrane potential If there is net flux, why don’t the ion gradients and thus membrane potential eventually change? Na/K pump Nernst equation+ Takes into account Nernst of ion + channel permeability If ion not at equilibrium, there’s some driving force for ion to move in certain direction

Explain why Nernst equation doesn’t work at low extracellular K concentration K channels have highest permeability, dominant contributor to membrane potential, therefore not linear as with Nernst potential. As you move to lower external K conc, conc gradient isn’t changing too much so see plateauing effect. Nernst potential of common ions: Na: +55mV Cl: -65mV K: -90mV

Mercer Lectures How does a cell move molecules across an impermeable membrane? How is this regulated? Why do our cells even have all these ion channels, pumps, and exchangers? What makes our strategy better than other organisms? Any limitations? Why do our cells expend so much energy on this Na,K-ATPase? Clinical relevance? How have we used our understanding of membrane transport in the clinical setting (e.g. disease mechanisms, drug resistance, development of SGLT2 inhibitors for diabetes)? KNOW your epithelial cell junctions (location, components, diseases, etc) Polarity is a critical feature of epithelial cells, but why it this useful? Once polarized, how do they know how to get the right proteins to the right place? Specific modes of membrane transport – membrane is a pretty good barrier, good at keeping things in/out. But it still needs to take in/get rid of particular molecules at the appropriate times. How can this impermeable barrier achieve this? Especially when trying to move things against their concentration gradient? How does it differ based on the molecule you’re trying to transfer? Think about passive vs active transport and when those are necessary? 2) Hold your wee for a wii example. Why do the rabbits die? 3) Na/K pump – maintaining this gradient is critical for a variety of cell functions. But cell is actively expending a ton of energy/ATP constantly to push Na out and bring K in. Why do this? Clinical applications? 4) Membrane transport and disease/drug development. I REALLY like clinical applications. 5) Epithelial cell junctions – what proteins are involved? What happens if there’s a defect in one of them? Implicated in a lot of diseases. Maybe pick a few of your favorite but don’t memorize absolutely everything. 6) Epithelial cell polarity – v important physiologically. If either side of the cell is contacting a different environment (e.g. kidneys, intestine, etc), want to regulate what goes in/out either side. But how does cell know to put the right proteins on the right sides?

Nichols Lectures How do ion channels maintain specificity for their ion? What is the membrane potential? Why do cells have one? Nernst vs GHK What’s happening at each stage when an action potential is fired? Channelopathies - clinical importance of mutations in the KATP channel and insulin secretion There was a lot of structure and topology in this lecture. Interesting but won’t be asking anything in depth on this. Self-explanatory Went over in first few slides. Don’t need to calculate but understand conceptually what information each tells you. Know what channels are involved. What’s happening in these channels? Know this mechanism inside and out. Great example of the severe disease you can get with disruption of a single channel. Think about what does this channel do normally? How do mutations affect this channel? How does channel activity link to disease phenotype?