1. Electrical Properties of Human Cells 17.1.13

2. Cell membrane Cells are basic building blocks of living organisms. The boundary of animal cells is a plasma membrane composed of thin phospholipid bilayer and proteins embedded in it The main role of the cell membrane is to regulate the exchange of chemical substances Fluid mosaic model of S. J. Singer and Garth Nicolson 1972 best describes structure of membranes bilayer.

3. Fluid Mosaic Model of a Cell Membrane Cell membrane is a phospholipid bilayer, i.e. a layer which is only two phospholipid molecules thick. Each of these molecules has two ends (one is a phosphate group, the other a hydrocarbon chain, i.e. a lipid) and these two ends have very different properties The phosphate end is polar and thus hydrophilic (it likes to be in a watery environment and to be surrounded by water molecules). In contrast, the lipid end is hydrophobic (it hates to be close to water;

4. Non polar regions of phospholipid molecules in each layer face core of bilayer and their polar head groups face outward, interacting with aqueous phase on either side.

5. Proteins are embedded in this bilayer sheet. Peripheral proteins exist on the surface of the bilayer while integral proteins are embedded in the bilayer. Some proteins protrude from only one side of membrane; others have domains exposed on both sides The individual lipid and protein units in a membrane form a fluid mosaic with a pattern that is free to change constantly. The membrane mosaic is fluid because most of the interactions among its components are noncovalent, leaving individual lipid and protein molecules free to move laterally in the plane of the membrane Fluid Mosaic Model of a Cell Membrane

6. Integral proteins are held by hydrophobic interactions between membrane lipids and hydrophobic domains in the proteins The integral proteins which completely span the bilayer and exist in pairs forms a protein channel which are watery pathways

7. Mechanisms of Transport across Cell Membrane Facilitated diffusion Transmembrane proteins create a water-filled pore through which ions and some small hydrophilic molecules can pass by diffusion. The channels can be opened (or closed) according to the needs of the cell. Active transport Transmembrane proteins, called transporters, use the energy of ATP to force ions or small molecules through the membrane against their concentration gradient

8. Protein Channels in Cell Membrane Protein channels can either be gated or non-gated (leakage channels) The transmembrane channels that permit facilitated diffusion can be opened or closed. They are said to be "gated“. Gated channels can be opened or closed like gates. Gates are gate like extensions of channel proteins which change their conformation under specific conditions These channels can be Voltage gated Mechanically gated Chemically/Ligand gated

9. Electrical Properties of Human Body The main chemical components of our body is water, salts (their ions) and some organic components such as proteins, lipids and so on Current flow in human body is caused not by the movement of electrons but by that of ions in water (electrolyte) The electric signals produced by cells are carried by ions rather than electrons. Electrical impulses in living cells do not travel at the speed of light as electrons do

10. Electrical Properties of Membranes Pure phospholipid bilayers are quite good insulators (there are no free ions in the membrane so there are no carriers to transport charges) Membranes act as barriers to the free diffusion of various substances including ions. Phospholipid bilayer is itself highly impermeable to ions The high conductance of biological membranes even at rest (i.e., without synaptic influences etc) is mainly due to protein channels which penetrates the membrane and allow ion currents to flow across the membrane

11. Charge Carriers Across the Membrane (ions) Mainly Na +, K + and Cl - Other ions include Mg ++, Ca ++,HCO 3 -, NH 4 + or phosphate ions Ions pass through protein channels that are selective for that specific ion

12. Membrane resistance Since electric current in an aqueous solution is a flow of ions, the relatively low mobility of ions through the lipid bilayer is equivalent to a high electric resistance. Membrane resistance is a measure of ease with which ions move across the membrane under the influence of a potential difference Ion channels acts as resistors however, since they are characterized as being open or closed, thus they are variable resistors

13. Resting Membrane Potential Under resting or unstimulated condition, there exists an electrical potential difference across the cell membrane with the inside negative relative to the exterior. Typically -70 mV (-40 to -90 mV) membrane is said to be polarized

14. The cell membrane separates interstitial fluid from intracellular fluid (ICF). The two fluids (inside and outside) are both electrically neutral but they contain many different kinds of ions The cell interior tends to have a much higher concentration of K+ than exists outside the cell. These positive ions are electrically balanced by large negatively charged proteins ((membrane is impermeable to them, A - ) Outside the cell, there is a much higher concentration of Na+ than inside. These positive ions are electrically balanced by negatively charged chloride ions (Cl-) and small amount of other anions ECF and ICF are electrically neutral

15. Sources of Membrane Potential Na+/K+ pump Nature of the membrane: Selective permeability Gibbs–Donnan effect

16. Role of Na+/K+ pump in establishing resting membrane potential A major contribution to establishing the membrane potential is made by the sodium-potassium exchange pump. This is a complex of proteins embedded in the membrane that derives energy from ATP in order to transport sodium and potassium ions across the membrane. On each cycle, the pump exchanges three Na + ions from the intracellular space for two K + ions from the extracellular space. If the numbers of each type of ion were equal, the pump would be electrically neutral, but, because of the three- for-two exchange, it gives a net movement of one positive charge from intracellular to extracellular for each cycle, thereby contributing to a positive voltage difference.

17. The pump has three effects: (1) it makes the sodium concentration high in the extracellular space and low in the intracellular space (2) it makes the potassium concentration high in the intracellular space and low in the extracellular space; (3) it gives the extracellular space a positive voltage with respect to the intracellular space. Role of Na+/K+ pump in establishing resting membrane potential

19. Nature of the membrane: Selective permeability Cell at rest is hundred folds more permeable to K+ than to Na+ through passive nongated leakage channels There is a greater tendency of K+ ions to move out of the cell than of Na+ to move into the cell When more positive ions move outward than inward, the inside of the membrane becomes electrically negative than the outside. Thus an electric potential difference develops across the membrane

20. Gibbs–Donnan effect The Gibbs–Donnan effect (also known as the Donnan effect) is a name for the behavior of charged particles near a semi- permeable membrane which fail to distribute evenly across the two sides of the membrane The usual cause is the presence of a different charged substance that is unable to pass through the membrane and thus creates an uneven electrical charge. For example, the large anionic proteins in intracellular fluid are not permeable to cell membrane. They attract positive ions across the membrane which cal also not penetrate membrane

21. Resting Membrane Potential When the cell is at rest, gated channels are closed and it is mainly K+ ions that flow across the membrane (through leakage channels). By convention, the ion that determines the so-called "resting" membrane potential of a cell, is potassium, although other ions do contribute in more minor ways. By convention, the electric potential of the outside of the membrane is normally taken as the reference point (or zero). The sign of the membrane potential is designated as the voltage inside relative to ground outside the cell. This means that the potential inside is negative. In the equilibrium state or the resting state the membrane potential is about -70mV, although it varies for different types of cells from about -40 to -90mV

22. Concentration and electric gradients An electric force develops due to the presence of membrane potential which acts on the ions The flow of ions across the cell membrane occurs as a result of these two gradients: concentration gradient and electric gradients. Concentration gradient moves K+ out of cell while electric gradient moves it inside the cell These two components to the motion of ions are passive transport because they need no input of energy

23. Equivalent circuit model for Plasma Membrane Protein channels acts as variable resistors The cytoplasm and interstitial fluid are the electrical conductors and they are separated by a lipid bilayer of the membrane which has an insulating property. This feature can be modeled as a capacitor. Capacitance for a cell membrane is about 1µF/cm 2 Membrane resting potential is indicated as a voltage source