The questions are about quantitive physiology, please provide specific calculation or explanation for each question.

Solve the following problems step by step, if for explanation, please give specific reasons

  1. Recreate a classic electrophysiology experiment, consider a simplified cell that exhibits the following characteristics:

The questions are about quantitive physiology, please provide specific calculation or explanation for each question. 1

cell surface area= 300 m2, cell volume = 400 m3

temperature = 310k,

kBT/e (e-absolute value of charge of electron)= RT/F= 2.67E-2 (at T= 310k)

membrane capacitance =1 F/cm2

now dilute the extracellular fluid with water, cutting the bulk concentration of Na+, K+ and Cl- in the extracellular space in half (to 72.5, 2.5 and 58mM respectively). Assume the internal and external bulk concentrations of ions do not change any further in this question

The following question capture changes of an action potential in this modified extracellular environment, not capture the full dynamics, just key features

  1. What are the Nernst potentials and resting conductances for Na+, K+ and Cl- after dilution of the extracellular environment? Provide numbers for the entries marked with “???” in the table below, and show the calculation for them

The internal concentrations of ions do not change

The questions are about quantitive physiology, please provide specific calculation or explanation for each question. 2

  1. What are the resting potentials of this system before and after switching the extracellular solution? Use the pump-leak model, and assume the intracellular concentrations do not change. Also assume the membrane has had time to reach a steady state, the Na+/K+ antiport carrier is still active, and the ion conductances are as stated in the table.

  2. At some time point t=0 which is after the cell has had time to reach a new resting state in the diluted environment, a new Na+ channel opens, increasing total Na+ conductance to 50X the original. This new channel opens instantaneously, and stays open. Provide an equation describing membrane potential as a function of time following opening of this channel. Your expression should only have t as a variable, with all other values specified.

  1. Cardiac muscle cells usually maintain a low internal concentration of Ca2+, and small increases lead to contraction of these cells. A large contributor in the ability to maintain these low internal Ca2+ concentrations is the presence of a Ca2+/Na+ antiport pump, which couples Na+ import with Ca2+ export. As with most cells, the Na+/K+ pump is also present in these cells at significant amounts, and is largely responsible for creating the Na+ concentration gradient.

Answer: Given these concepts, explain in a few sentences why the drug oubain, which inhibits the Na+/K+ pump (30-40%, but introduces side effects at higher doses), is often used to treat heart failure?

  1. Remodeling of actin filaments is central to many structural changes in cells

The questions are about quantitive physiology, please provide specific calculation or explanation for each question. 3

The questions are about quantitive physiology, please provide specific calculation or explanation for each question. 4

consider the process of actin polymerization-based protrusion of the cell edge, assume:

  • The rate of edge protrusion is equal to the rate than an actin filament grows at the plus end, the rest of the filament remains stationary;

  • Consider that only ATP-actin is around, there is no ADP-actin considered in this problem;

  • Actin filaments consists of dimers of actin molecules, each of which measures 5-nm in length, addition of a new actin molecule to the end of a filament extends its length 2.5nm

  • Use the average values of rate constants from the above table

Answer: What concentration of ATP-actin monomer in the solution surrounding the filament would produce a protrusion rate of 20 nm/sec?