Introduction to Biological Psychology Part III Chapter 4 Electrophysiology Electrical Signalling in the Body

NEURONAL 163 PART III NEURONAL COMMUNICATION Having learnt how the nervous system is made up of cells and structures that receive , process and pass on information to select and generate behaviours , we are now going to learn how neurons actually perform this key function , by interrogating the mechanisms by which they receive , integrate and generate signals in order to communicate with each other .

I 165 . ELECTROPHYSIOLOGY ELECTRICAL SIGNALLING IN THE BODY Catherine Hall Learning objectives By the end of this chapter , you will understand common electrical terms and how they relate to electrical signalling by neurons understand the ionic basis of the membrane potential .

166 Key electricity concepts Neurons signal electrically . They receive inputs from other cells , sum up all these inputs , and generate an electrical impulse , called an action potential , which they send along their axon . Neurons are not the only cells that to use electricity to function . Muscle cells also use electrical signals to constrict and dilate . We will be going into some detail to understand how neurons are able to use electricity to signal in this manner , but it worth going over some key electricity ' Electrical currents are of charged particles . In an electrical circuit in a torch , where a battery powers a lamp ( Figure ) the charged particles are negatively charged electrons in a wire . In your body the charged particles are ions such as the sodium ion , Charged particles because they are repelled by similar charges and attracted by opposite charges , positively charged particles attract negatively charged particles , while negatively charged particles repel other negatively charged particles , and positively charged particles repel other positively charged ' Charged particles only if they can pass through the substance that they are in . Electrons can only How around an electrical circuit when the circuit is complete .

167 If the circuit is broken by opening a switch , because the electrons can easily pass through air , they can any more and the torch lamp will go off . The ability of a material to let electricity through it is termed conductance . The inverse of conductance is resistance a measure of how much a material resists the How of electricity . Voltage is a measure of how much potential there is for charged particles to How and is a measure of stored electrical energy . This electrical potential is analogous to storing water high up in a water tower . Because of gravity , the water has lots of potential to How , but it can not do this until a tap is opened . When a tap is turned on water flows out ofthe pipe ( Figure ) A battery works like a water tower to store electrical energy . Batteries have a positive and a negative pole . When a circuit is connected , electrons are repelled from the negative pole towards the positive pole of the battery .

168 I ELECT ?

AL ( Li Pol me mamas ' was mars we we Va Ex ve we ' a we awful swim VOl Fig . Electricity . A ) A battery powers a lamp by providing a source of negatively charged electrons which from the negative pole of the battery towards the positive pole , through a wire . When the circuit is broken by opening the switch , electricity can not flow . Electrical currents are analogous to water flowing through pipes . Water stored in a water tower has the potential to flow when a tap is opened . The rate of will depend on the stored potential ( how high the tower is ) as well as how wide the pipes are ( how much resistance to flow there is ) The current in a circuit is related to the Voltage across the circuit and the conductance or resistance of the wires making up the circuit , according to Ohm Law .

I 169 Current is proportional to voltage and conductance , and inversely proportional to resistance Current Voltage Conductance OR Current Voltage I Resistance You can come back and look at Ohm law later when you start thinking about currents in neurons . As you can see , if resistance goes up , and the voltage stays the same , the current ( How of charged particles ) will decrease . Conversely when the resistance goes down , the current will increase . In the water pipe analogy ( Figure ) high resistance is like having narrow pipes . If the hole in the middle of the pipe is tiny , you won get very much water squirting out , never mind how big the water pressure is , but if you make the hole bigger ( increasing the conductance or reducing the resistance ) a lot of water will flow out of the hole . As the water

170 I tank empties , however , the water pressure ( voltage ) decreases , and the water flow ( current ) will reduce . Nerves conduct electricity more slowly than wires Electrical currents in the body are not exactly the same as electrical currents in a wire . In 1849 , Hermann von measured the speed that electricity flows in a frog sciatic ( leg ) nerve , by stimulating it electrically at one end and measuring the electrical signal at the other end . He found that the speed that electricity ( or was conducted ) down a nerve was , around a million times slower than electricity travels through a wire . 30 why is electrical signalling in nerves so much slower than in wires ?

In a wire , electrons ( small negatively charged particles ) travel along the wire , and they can do this very quickly in materials like metals that conduct electricity well . In nerves , however , the charged particles are ions , not electrons . They are positively ( or sometimes negatively ) charged particles that are much bigger than electrons , and they don move down the nerve like electrons do . Instead , during a nerve impulse termed an action potential positively charged ions move into the neuronal axon from the outside . When positive ions move into the cell , the inside of the cell becomes more positive . This little bit of the axon becoming more positive triggers

171 positive ion movements into the next little bit of the axon , which also becomes positive , triggering the ion movements across the next bit of axon , and so on , like a Mexican wave of a positive potential along the nerve . On balance there has still been an electrical signal that moved from one end of the axon to the other , but it has got there more slowly than if electrons had just travelled along the wire . wwe Amn Fig . Electrical signalling in wires nerves

172 A short history of The importance of electricity in animating our bodies a step , in a way , towards generating behaviours was discovered in the century by Lucia and Luigi . Fig . Lucia 173 In a laboratory in their home , the couple discovered that electricity applied to a frog leg made the muscle twitch . The frog leg muscle also twitched when it was connected to the nerve with a material that conducts electricity . They concluded that an animal electricity is generated by the body to contract muscles . Fig . Luigi The study of how electricity is generated and used by the body is now termed electrophysiology . Animal electricity was further studied and made ( in ) famous by the ' nephew , Giovanni , who performed public demonstrations electricity on the bodies of executed prisoners as well as oxen heads . Tales of these demonstrations of Galvanism inspired the young Mary Shelley to write Frankenstein , in which the monster is animated using electricity .

174 I ELECTROPHYSIOLOGY and , to record the time course of the action potential for the first time in 1868 . He showed that the action potential was in duration and that , at its peak , the voltage rises above zero . also measured the resting membrane potential as being around , building on ideas developed by Walther , who proposed that the resting membrane potential is set by the potassium conductance of the membrane . Charles Ernest added to this the concept that sodium and potassium exchange is critical for the excitability of cells . The ionic basis of the action potential was fully between 1939 and 1952 by Alan and Andrew , who used the squid giant Fig . The action potential axon to make the first recorded in squid giant axon by and in 1939 of the action potential . They developed the use of the voltage clamp , which uses a feedback intracellular recordings

176 I ELECTROPHYSIOLOGY I 177 Squid giant axon A 178 I ELECTROPHYSIOLOGY ELECTROPHYSIOLOGY I 179 180 channels working as well , are not as able to action potentials to inhibit excitatory neurons which become overactive , causing seizures . How do cells such as neurons signal electrically ?

Cells signal electrically by controlling how ions cross their membranes , changing the voltage across the cell membrane . This voltage change across the cell membrane is the electrical signal . The most common ions that move across the cell membrane to cause this voltage change are sodium ions ( potassium ions ( chloride ions ( and calcium ions ( These ions carry different charges sodium and potassium ions each have a single positive charge , chloride has a single negative charge , and calcium ions carry two positive charges . Positively charged ions are called , while negatively charged ions are called . The amount of charge carried by an ion is its valence .

181 In addition to carrying different charges , ions are different sizes . A mu ( Some ion How , 01 ' Fig . Ions are different at rest and her . happens during signalling . In this section , vve consider what going on at rest , and in the next section , examine what happens to make an electrical signal . The plasma membrane around a cell is made of a Cells are surrounded by a plasma membrane that keeps the inside separate from the outside . This mummy ma ol cel membrane is made of Fig . two parallel layers of molecules Called molecules ) have three main parts two fatty tails that are hydrophobic ( meaning they fear water ) and a head that is hydrophilic ( meaning it loves water ) Water molecules are slightly charged , with positively charged and negatively charged zones ( they are ) This means that other particles that are charged are attracted to

182 them , whereas particles with no charge are repelled by them . The head carries a negatively charged phosphate group , so is attracted to water , while the uncharged fatty tails are repelled by water , but will happily mix with other uncharged tails . This means that the molecules line up to form a ( two parallel layers molecules ) with their fatty tails next to each other on the inside of the membrane , and the hydrophilic heads lined up facing the watery inside and outside of the cell . Small molecules such as oxygen and carbon dioxide can diffuse across the membrane , but because the inside of the membrane is uncharged and hydrophobic , water and other charged particles can cross it . This means the inside of the cell is kept separate from the outside and the intracellular , or , inside the cell can have a different constitution than the fluid outside the cell the extracellular .

183 Components of intracellular extracellular fluid Extracellular woo game Intracellular ( and , en , extracellular ( are I , 50 made up of different . mo substances ( Figure ) In Both are mostly water , but Intracellular the concentration of ions Fig . Constituents of and and other substances is very different . Of particular note , there is a higher concentration of potassium ions inside the cell compared to outside the cell ( inside outside ) and a high concentration of sodium ions outside the cell compared to the inside of the cell ( outside inside ) There are also more chloride and calcium ions outside the cell than inside the cell . also contains more protein and a higher concentration of organic than .

184 Ion channels and transporters allow , substances to Fig . Transporter proteins shuttle molecules across the cross the membrane membrane If the cell membrane was just made up of the and nothing else , then no ions would ever be able to cross the membrane , and no electrical signalling would be possible . However , lots of proteins are embedded in the lipid membrane . Some of these are transporter proteins that can shuttle molecules across the membrane ( Figure ) For example , glucose is brought into the cell via glucose transporters .

As well as transporters , ion channels are also proteins that are embedded in the plasma membrane ( Figure ) These proteins form a pore in their centre which essentially makes a hole in the membrane . They can be open all the time ( leak 185 Fig . Ion channels form a pore in the membrane through which certain ions can pass to cross the membrane . channels ) or opened by different triggers , such as voltage changes ( ion channels ) or binding of different molecules ( ion channels ) Many of these ion channels are selective , they only let certain ions through . Examples of selective ion channels include potassium leak channels or sodium , potassium or calcium channels . This ion selectivity means that cells can control ion across their membranes by opening certain ion channels .

186 I The resting membrane potential ( belt Fig . Potassium ions are at a higher concentration inside the cell , but some can move out of the cell , down their concentration gradient , through potassium leak channels . At rest , in the absence of any neuronal signalling activity , it turns out a certain type of ion channel potassium leak channels are open . This means that , at rest , potassium ions ( can leak out of the cell . Because of the concentration gradient across the cell . because . there are more ions inside the cell as they wiggle and jiggle and randomly move about , some ions will these holes in the membrane and pass through them to exit the cell ( Figure 313 ) Once some positively charged ions have left the cell , however , that leaves an imbalance of positive and negative charges on the inside of the cell . The inside of the cell is now more negatively charged compared to the outside of the cell . There is now a voltage , or potential difference across the cell ( Figure ) which we could think of as an electrical gradient .

187 But ions are positively charged , so they are attracted to negative charges and repelled by positive charges so Once there is a Fig 314 Positively charged potential difference Or potassium leaving the Cell sets electrical gradient across the up all gradient . The inside ofthe Cell is negative with respect to the ions are repelled by the outside of the cell , stopping more potassium ions from leaving . cell membrane , the positive charge outside of the cell , and attracted to the negative charge inside of the cell . For ions , the electrical gradient therefore works in the opposite direction to the concentration gradient . The concentration gradient of , with high concentrations inside the cell and low concentrations outside the cell , tends to make ions leave the cell , while the electrical gradient tends to make ions enter the cell . We call the combination of the effect of the electrical and the concentration gradient an electrochemical gradient . This movement of ions out of the cell through leak channels is the main driver of the resting membrane potential of the cell the voltage difference across its membrane at rest which is around in neurons .

188 Equilibrium potentials EK ions will leave the cell down the concentration gradient until the electrical gradient is so negative that ions are stopped from leaving . At this point is in equilibrium the number of ions leaving because of the Fig . Equilibrium potential concentration gradient is for potassium the same as the number entering due to the electrical gradient , so there is no net movement of across the membrane . The voltage difference across the cell at which this equilibrium is reached is called the equilibrium potential for a given ion . It is dictated by the concentration difference across the membrane and the charge of the ion . We can consider different ions and how their electrochemical gradients shape the equilibrium potential for each . As we saw above , because is positively charged and is at a higher concentration inside the cell , it tends to leave the cell when channels permeable to are opened in the cell membrane . Positive ions leaving the cell make the cell membrane potential ( the electrical gradient or voltage

189 difference across the cell membrane ) more negative . The membrane becomes more and more negative until it reaches the equilibrium potential for when there is no longer any net ( flow ) of . Therefore the equilibrium potential for is negative . For most cells , it is around . This is often written as EK ( or the electrical potential for ) There is more sodium ( Nal ) outside the cell than inside the cell , so if ion channels that are permeable to Nal open in the membrane , sodium will tend to enter down its concentration gradient . is positively charged , so initially it is attracted to the Fig potential negative potential on the inside of the cell . entry makes the inside of the cell more positive , though , until enough has entered to make the inside of the cell so positive that it repels further entry . it reaches equilibrium . This happens at around 62 . Therefore the equilibrium potential for ( the electrical potential across the cell where there is no net flux of ions ) is .

190 I Fig . Equilibrium potential for Chloride There is more chloride ( outside the cell than inside the cell , channels that are permeable to membrane , tends to enter the cell . As is negatively charged , its entry so when ion open in the makes the cell membrane potential more negative , until it reaches equilibrium , being negative to repel further entry . This happens at around , so . The Equation We can mathematically calculate the equilibrium potential for different ions using the Equation .

191 Universal Gas Temperature Constant , in Valence Faraday ( charge on VON ) Fig . The Equation This equation might look complicated , but if we break it down we can see that it just relates the concentration gradient across the membrane of an ion ( in , Where is the concentration of the ion of interest ) and the charge or valence on that ion ( to the equilibrium potential ( and are just constants , and is the temperature , which is constant inside the body , so we can ignore , and here , as they will always stay the same .

192 and the Equation To understand the Equation fully , we also need to understand what In means . This is an instruction , which means take the natural log of the number inside the brackets . In this case , that number is the ratio of the outside and inside concentrations ) The log of a number is the powerto which a base number has to be raised to equal the original number . The base number can be anything . in the first example below , we are using base 10 , but in the case of the natural logarithm ( In ) it is a specific mathematical constant called or constant . it roughly . Example to the base 10 is the power to which 10 must be raised to equal , so is the log to the base 10 ( logo ) of (

193 Example to the base ( natural ) In the equations below , is the power to which must be raised to equal , so is the natural log ( In , also written loge ) of . More about and powers Raising a number to a positive power makes it bigger , whereas raising a number to a negative power makes it smaller ( means the same as means the same as ) Conversely , the log of a number between and is negative , and the log of a number is positive . For example ( using 10 as the base , not , to make the sums clearer ) 102 100 ( 104 ( You can find more background on powers and . We can now look at , and and see how their equilibrium constants come out of this equation , even just by broadly considering the

194 charge of the ion and whether there is more of an ion on the inside or outside ofthe cell . EK There is more inside the cell than outside the cell , so ( The natural log of is negative . We then need to multiply this by the charge , which is for . Therefore the equilibrium potential , EK , is negative . EN There is more Na outside the cell than inside the cell , so ) The natural log of numbers greater than is positive , and this is multiplied by the charge of for . Therefore the equilibrium potential , is positive . There is more outside the cell than inside the cell , so ( The natural log of numbers greater than is positive , but this is then multiplied by the charge of for CI . The equilibrium potential , is therefore negative .

195 The membrane potential We have discussed that when the cell is at rest , potassium leak channels are open and this drives the resting membrane potential to be negative , at around . But we also just saw the equilibrium potential for potassium is . If the resting membrane potential is set by potassium through leak channels , why is the resting membrane potential not the same as EK ?

The answer is that at rest the membrane is actually also a tiny bit permeable to as a small number of sodium channels are also open . This pushes the resting membrane potential a tiny bit away from the equilibrium potential for potassium towards the equilibrium potential for sodium . The resting membrane potential is closest to EK as the membrane is most permeable to ions ( more channels are open ) but is a bit more positive than EK because of the small amount of permeability at rest to ions . In Fact , at any point during neuronal signalling or at rest , the membrane potential is set by the electrochemical gradients to different ions and the relative permeability of the membrane to these ions . Cells control their membrane potentials by opening and closing ion channels in the membrane to alter the permeability to different ions , which then flow down their electrochemical gradients into or out of the cell . When sodium channels open , for example , the permeability to increases and ions enter the cell , driving the membrane potential to more positive potentials towards the equilibrium potential

196 for , When sodium channels close , the permeability to decreases again and , as the membrane is now more permeable to than , the membrane potential will again become more negative , returning to the resting membrane potential . There are lots of types of ion channels that are selective for different ions and have different gating properties , they are opened and closed by different stimuli , such as changes in membrane voltage , and binding of molecules . We discuss these more in later chapters . The The equation allows the . Na . membrane potential of the NaA ' cell ( Em ) to be calculated from the of the membrane to different Fig . The ions ( and for and equation respectively ) and their concentration gradients ( Figure ) As for the equation ( see Box , Figure ) and are constants , and is temperature , so can be considered unchanging . During neuronal signalling , the permeability of the membrane to different ions changes , and the membrane potential is

197 weighted in favour of the equilibrium potential of the ion with the greatest permeability at that moment . Note that the concentration gradient is expressed in reverse compared to and , to account for the fact that , being negatively charged , it is oppositely charged to and . The We have seen above that during rest and neuronal signalling , ions flow through ion channels down their electrochemical gradients , altering the membrane potential . This How of ions down their electrochemical gradients does not require any energy . The membrane potential is controlled by changing the permeability of the membrane to different ions , and not by changing the concentration gradients between the inside and outside of the cell . Very few ions need to How to change the membrane potential of a cell , which means that the concentrations of ions inside and outside the cell do not change very much over the short term . However , because the membrane potential does not sit at the equilibrium potential for any ion , even at rest , there is a net current or out of the cell and , a net into the cell . Over the longer term , however , these would dissipate the ionic concentration gradients if cells did not have a mechanism to continually pump ions back to where they came from . The pump that does this really important job is the pump , or the . This is a

198 ELECTROPHYSIOLOGY protein that sits in the plasma membrane and pumps sodium out of the cell and potassium back into the cell . Because this pumping occurs against the ions electrochemical gradients , it requires energy in the Form of to pump the ions back and maintain their concentration gradients . The potassium removes a phosphate group from , to form , releasing some energy , which changes the shape ( or conformation ) of the enabling it to move ions out of the cell and ions into the cell for every molecule used . Because ions are removed for every ions brought into the cell , the is , causing a net export of positive charge . This contributes a little bit to the negative resting membrane potential , but by far the strongest effect the has on the resting membrane potential is to maintain the potassium electrochemical gradient , so that the equilibrium potential for potassium is maintained . Because even at rest there are ion , the is always at work , but it activity is increased when neurons are signalling and so more ions need to be pumped back .

Figure . Across one cycle of activity , ions are transported out of the is to and phosphate ( Pi ) and ions are transported into the cell . 199 Maintaining ion concentration gradients is so important for sustaining neuronal activity that the is the single most process in the brain , consuming over half of all the energy it uses . As the brain is a very energetically expensive organ , using 20 of the body energy at rest , despite comprising only of the body mass , the alone uses over 10 of the energy used by the whole body quite staggering given there are over different types of proteins in our bodies at any one time !

200 Key Takeaways Electrical signalling in neurons ( and other cells ) works because they have ion channels that allow specific ions to flow across neuronal membranes and change the membrane potential of the cell . The membrane potential of the cell is determined by the concentration gradient of ions across its membrane , and the permeability of its membrane to those ions . Ions down their electrochemical gradients , which does need any energy , but energy in the form of must be used up to fuel the which pumps ions back up their electrochemical gradients to maintain their concentration gradients across the membrane .

201 About the Author Catherine Hall UNIVERSITY OF Catherine Hall is a member of the Neuroscience Steering Committee , the University Senate , convenes the core first year module , and lectures on topics relating to basic neuroscience , neurovascular function and dementia .