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BB101: Biology for Engineers (2016)

Module-3
Tutorial-1

Section A: Nernst and GHK equations

A1. Typically in our tissues, the ECF concentration of Ca++ ions is 2.5 mM. ECa is known to be +140 mV.
Calculate [Ca++]i , i.e. the intracellular concentration of Ca++ ions in our cells.
A2. Note the magnitude of [Ca++]i calculated in A1. This tells you our cells prefer to maintain their internal
Ca++ at extremely low levels, especially when compared with other ions. What could be the possible reason
for this? A large number of intracellular processes depend in a highly sensitive fashion upon the exact value of
[Ca++]i (and its temporal dynamics). Can you think of (or find out about) some such processes?
A3. The chemical activity of an ion in solution is a more accurate estimate of its availability (for processes such as
diffusion and pumping, for instance), than its concentration. Ion-sensitive electrodes have been developed that can
reliably measure intracellular activities of various ions. For example, intracellular chloride activity (denoted iaCl)
of smooth muscle cells was measured using Cl-sensitive intracellular microelectrodes, and was found to be 45
mM. The following information is also available:
Resting membrane potential = 66 mV; oaCl (extracellular Cl activity) = 110 mM.
(i) Substituting activities for concentrations, calculate ECl using R=8.314 J/K-mole, T=37 oC (since the
experiments were done on mammalian (guinea-pig) muscle), and F=96,500 Coul/mole.

(ii) Is Cl at equilibrium across the smooth muscle cell membrane? If not, what would require to be the value
of iaCl in order for Cl to be at equilibrium?
(iii) Suppose a neurotransmitter acts on the smooth muscle cell membrane to open channels that are
specifically permeable to Cl. Will the membrane potential of the cells change? In which direction?

A4. In a nerve cell, at the peak of the action potential, PNa is observed to have increased to 400 times its value at
rest, PK not to have changed, and PNa/PK to be 12. Take [Na]o=120 mM, [Na]i=10 mM, [K]o=5 mM, [K]i=140
mM, temperature to be 27 oC, R=8.31 J/(K-mole), and F=96,500 Coul/mole. What was the resting membrane
potential of the cell? What was the membrane potential at the peak of the action potential?

A5. The squid giant axon (s.g.a.) is a very convenient experimental model for electrophysiological studies
since it allows easy measurement of ionic concentrations. For instance, the external ionic composition is the

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same as that of sea-water, the squid being a marine aquatic animal. The following are the respective
concentrations (in mM) of Na, K and Cl in sea-water: 460, 15 and 545. Intracellular concentrations can be
easily estimated because the giant axon can be literally squeezed with a small roller, extruding the axoplasm
(axonal cytoplasm) much as one might squeeze toothpaste out of a tube. The following concentrations are
found in the axoplasm (in mM): Na 50, K 400, Cl 36.
Assume experiments are performed at 20oC. Take the universal gas constant R as 8.314 J/K-mole and
Faraday's constant as 96,500 coul/mole.
(i) Determine the equilibrium potentials for Na, K and Cl in mV.

(ii) Given that at rest: PK = 40 PNa and PK = PCl determine from the Goldman-Hodgkin-Katz (GHK) equation
for Na, K and Cl the transmembrane potential (Vm) at rest.
(iii) Which ion is closest to equilibrium at rest? Why?

(iv) If PCl is increased, will there be significant transmembrane flux of Cl ions? In which direction? Why?
(v) If PNa or PK is increased, will there be significant flux of Na or K ions? In which direction? Why?
(vi) Suppose PCl increases 1000-fold. From the GHK equation, calculate the new steady-state value of Vm.
(vii) Ignore Cl in the GHK equation and calculate Vm based on the expressions for Na and K.
(viii) Compare the values of Vm obtained in (ii), (vi) and (vii) with each other and with ECl. Explain any
obvious relationship that you find.

(ix) What will be the new steady-state value of Vm if :

(a) Sodium permeability selectively increases 500-fold?
(b) PNa and PCl increase simultaneously 500-fold and 1000-fold respectively?
Think about the significance of answers in (ix).

Section B: Membranes as Electrical Circuits

We have seen in class that cell membranes can be considered from an electrical viewpoint to be R-C circuits,
as in the diagram below. This lends them to being treated mathematically in terms of such circuits. Cell
membranes Like any R-C circuit, the membrane will have a time constant, denoted by m. Consider following
questions to see the properties of m.

B1. Suppose a stimulus in the form of a step current is delivered, switched on at t=0, its magnitude being Is.
What will be the trend, with respect to time, of the voltage developed across the circuit?

B2. What equation will govern this trend?

B3. What will be the final value of Vm (at t = )?
B4. At an instant of time equal to m , to what value will Vm rise, compared to its final value?
B5. Suppose the current is switched off at t=t. What will be the trend of the voltage across the circuit?
B6. At an instant of time equal to m after t, what value will Vm have attained, compared with its value at t=t?
B7. In a time equal to 5 m after t, what will be the percentage value of Vm, compared with its value at t=t?
B8. A neuron has Rm = 1 K-ohm, Cm = 1 F. Calculate the time constant.
B9. You have two cells, A and B. Cell A has a m of 5 ms, while cell B has a m of 10 ms. Which cell will
attain threshold for AP earlier? (Assume both cells have the same threshold for the AP).
B10. Will the m values of the two cells also determine the dynamics of the respective action potentials in the
cells? Why or why not?