BB101 Lecture 1-2- SM 2015

S. Mukherji, IIT-Bombay (mukherji@iitb.ac.in)

Ground Rules

• Lectures as scheduled • Tutorials as scheduled – there might be a quiz in one of

the tutorial sessions (10 minute quiz). o No repeats of class lectures in tutorials. o If you have doubts – post on moodle by Sunday – answers will be

posted or discussed in all the tutorial sections of that week. o Material covered in tutorials will be associated with the lectures

and will be part of the exam syllabus.

• Quiz o Strict about time… land up by 0815

• Mid Sem o End sem for tis part will be short answer type and small

numericals.

Syllabus

• Biomedical Innovations • Cell Membrane, Resting Membrane Potential • Action Potential • Nerve conduction • Heart – Electrical and Mechanical activity • Endocrine system • Insulin and diabetes mellitus

Where to get reading material ???

• CLASS NOTES……VERY IMPORTANT • Lecture slides • Tutorial slides • Textbook of Medical Physiology by Guyton & Hall – you

can get it in the library. • Quantitative Human Physiology: An Introduction by

Joseph Feher (relevant portions) – difficult to obtain • Internet – but please treat that material with caution.

Biology l Engineering

The Sciences and Engineering

Engineering

Chemistry

Physics

Mathematics

New Definition

Engineering

Chemistry

Physics

Mathematics

Biology

Travelling far … what do you need ?

Fantasy – Science Fiction – Reality

Getting Ready – the tricorder challenge

Science o Biology l Engineering

The famous radiograph made by Roentgen on 22 December 1895. This is traditionally known as "the first X-ray picture" and "the radiograph of Mrs. Roentgen's hand. "

The great breakthroug came in 1913 when William Coolidge and Lilienfeld made there first hot filament Cathode X-Ray tube. They replaced the cold Cathode with a heated spiral filament Cathode and tungsten Anode. The third anticathode disappeared, the angle of the Anode in his tube was set at 45º. X-Ray's could now be better controlled and were more reliable. The only practical problem was cooling the Anode, (which got extremely hot) this was a huge problem due to it's small size. New designs were developed, a heavy copper base to the Anode, sometimes with water or air cooling, this conducted the heat away and therefore increased the capacity of the tube to withstand a high current.

Engineering o Biology

• Eindhoven was a physiologist… was interested in the electrical activity of the heart.

• Although electrical recordings of the heart were made earlier (Waller, 1887), in 1903 Einthoven demonstrated the first recordings of the ECG using an ingeniously built system with a high sensitivity Quartz filament for detecting ECG current.

Robert Langer

Chemical engg., chemistry

Degradable polymer for controlled drug release

Think big. Never give up!

Joint replacements

Mechanical engg, Materials sc. & metallurgy

Biology on engineering

Communication – the basis of organization

• Unicellular organisms survive on their own – so why evolve multicellular organisms ?

• By collaboration and by division of labor it becomes possible to exploit resources that no single cell could utilize so well.

o Initially simple association of cells o Later complex multicellular plants and animals

Many Types of Cells

Advances in optical and electron microscopes have enabled us to move in close to the cells and take wonderful images.

Cell to cell communication Direct contact

Local Signalling

Long distance signalling

A Human Cell

Muscle cells and Nerve cells - Specialists

• The muscle cell has made contraction its specialty. Its cytoplasm is packed with organized arrays of protein filaments, including vast numbers of actin filaments and mitochondria.

• The nerve cell stimulates the muscle to contract, conveying an excitatory signal to the muscle from the brain or spinal cord.

• Schwann cells are specialists in the mass production of plasma membrane, which they wrap around the elongated portion of the nerve cell, laying down layer upon layer of membrane like a roll of tape, to form a myelin sheath that serves as insulation.

Features of the Nerve Cell

• The nerve cell has to be extraordinarily elongated o After all it is carrying a signal from the brain to a “far off” muscle. o The main body, containing the nucleus, may lie a meter or more

from the junction with the muscle.

• The cytoskeleton has to be well developed so as to maintain the unusual shape of the cell and to transport materials efficiently from one end of the cell to the other.

• The plasma membrane, which contains proteins that act as ion pumps and ion channels, causing a movement of ions that is equivalent to a flow of electricity.

o All cells contain such pumps and channels in their plasma membranes, however the nerve cell has exploited them in such a way that a pulse of electricity can propagate in a fraction of a second from one end of the cell to the other, conveying a signal for action.

We deal with…

• Excitable Cells o Nerve cells (neurons; neurones) o Muscle cells

• Nerve and muscle cells come in several types o Neurons vary from one region of the nervous system to another o 3 types of muscles

� Skeletal (voluntary) � Cardiac (involuntary) � Smooth (involuntary)

Body electricity [biopotentials]

• Body surface potentials • e.g. ECG, EEG, EMG, EOG, EGG etc. • Based, at cell level, on “action potentials” and other

potentials • Cellular Biopotentials:

o Resting membrane potential � Steady baseline potential in all cells.

o Action potential � Transient signals responsible for carrying information within a

neuron.

o Synaptic potential � Transient in nature, mediates communication between two neurons /

between neuron and target cell.

Neuron

• Dendrites o Receiving stations of neurons o Don't generate action potentials

(classical notion) o May / may not generate action

potentials (new notion) • Cell body

o Site at which information received is integrated, generation of action

potential • Axon (only one)

o Transmission of action potential o Terminal

� Relays information to next neuron in the pathway / other target cell

Purves et al., Life: The Science of Biology, 4th Edition

Action potentials everywhere

http://www.emc.maricopa.edu/faculty/farabee/biobk/biobooknerv.html

http://www.backtohealthonline.com/emg.html

http://www.guthrie.org/services/cardiac/procedures/ekg.asp

http://www.biopac.com/Education.asp?Cid=429

Action potentials everywhere

Heart: ECG

Stomach: EGG

Skeletal muscle: EMG

Basic Structure of Biological Membranes

Ref. Quantitative Human Physiology by Joseph Feher

Membrane proteins in the lipid bilayer

Ionophores and Voltage/Ligand Gated Channels

Concentrations of Na, K and Ca and resting

membrane potential across muscle cell membrane

Ref. Quantitative H

uman Physiology by Joseph Feher

Energetics of Ion Movement

Electrochemical Potential for each ion in solution :

xxxxx zCRT \PP �� ln0

constant sFaraday' is energy potential electrical theis

potential no andmolarity unit ofsolution alhypothetic

a of potential chemical theissolution afor 0

Free energy change per mole for movement of ion from outside of cell to inside of cell is :

oxxoxoxixxixix

zCRTzCRT ,,0,,,

lnln \P\P

��

Forces generating the Na equilibrium potential Ref. Q

uantitative Hum

an Physiology by Joseph Feher

The Nernst Equation

The Equilibrium Potential across a membrane arises from the balance between electrical forces and mechanical (i.e. diffusion) forces. We can derive it either from the Fick’s laws of diffusion or from the energetics point of view.

oxoxix

oxxoxoxixxixixx

zCRTzCRT

,,0,,,

� �

�� '

For sodium ions at 37qC this translates to 61.5 mV per decade gradient.

Ion Concentrations and Resting Membrane Potential

Obviously since all these ions (and more) are present, there has to be effect by each one of them in developing the RMP. Nernst Equation does not explain it all

Mammalian muscle (rmp = -75 mV) ECF ICF

Cations Na+ 145 mM 12 mM K+ 4 mM 155 mM Anions Cl- 120 mM 4 mM

Frog muscle (rmp = -85 mV) ECF ICF

Cations Na+ 109 mM 4 mM K+ 2.2 mM 124 mM Anions Cl- 77 mM 1.5 mM

Where does a Nernst Potential develop?

Two solutions having different concentrations of a highly dissociating salt separated by:

A completely permeable (allows everything) membrane. A semi-permeable, i.e. allows only one ionic species, membrane An impermeable (i.e. allows nothing through) membrane.

Life is more complex

• Earlier we assumed a hypothetical membrane through which only one type of ion can pass through… but life is not so simple..

o Many other ions are also present and some of them may also pass o Membrane permeability to ions may be time varying.

• An outcome of integrating the Nernst-Planck Electrodiffusion Equation gives the Goldman-Hodgkin-Katz Equation…

º«¬

ª��

� ��

��

oCliNaiK

iCloNaoK

]Cl[P]Na[P]K[P]Cl[P]Na[P]K[P

lnRTEm

Equilibrium potentials for Na, K, and Cl in a

muscle cell

Ref. Quantitative H

uman Physiology by Joseph Feher

BB101 Lecture 1-2- SM 2015

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