THE PHYSIOLOGY OF EXCITABLE CELLS

Transcription

1 THE PHYSIOLOGY OF EXCITABLE CELLS Evelyn Morn Department of Electrcal & Computer Engneerng Queen s Unversty, Kngston, Ont. In all cells a potental exsts across the cell membrane due to dfferences n the onc composton of the ntracellular and extracellular meda. A specal class of cells called exctable cells are capable of self-generaton of electrochemcal mpulses (called acton potentals) at the membrane, whch can be transmtted along the length of the cell. Ths class of cells ncludes sensory and motor neurons (or nerve cells) and cardac, smooth and skeletal muscle cells. Acton potentals serve as a means of communcaton between exctable cells and result n actvaton of the contractle mechansm n muscle cells. Cell Membrane Structure 1 The cell membrane often called the unt membrane separates the cell from the outsde world. In mcroscopc mages, the unt membrane appears as two dense lnes separated by a space. Gven these mages and the knowledge that the membrane s composed prncpally of protens and lpd molecules, models of cell membrane archtecture have been developed. The currently accepted model s that the membrane s comprsed of a lpd blayer wth embedded protens, as shown below. Lpd molecule wth a polar (hydrophlc) head and non-polar (hydrophobc) tals. The polar heads are exposed to the aqueous ntracellular and extracellular envronments. Embedded protens the proten on the rght completely traverses the cell membrane and s called a transmembrane proten. Some transmembrane protens form channels through whch ons can move nto or out of the cell. The cell membrane s selectvely permeable,.e. t s more permeable to certan speces of ons than others. Because of the selectve permeablty of the cell membrane, a measurable potental, called the restng potental, exsts across the membrane. How the restng potental s generated s dscussed below. The Restng Potental The cell restng potental arses because the nternal envronment of the cell s electronegatve wth respect to the external envronment, resultng n an abrupt change of potental across the cell membrane. Ths s analogous to a charged capactor, where the lpd 1 Informaton for ths secton was obtaned from Membrane Structure and Functon, Gwen V. Chlds, Ph.D., at 1

2 matrx of the membrane acts as a delectrc. The separaton of ons s due to the selectvely permeable nature of the cell membrane. The Donnan Equlbrum Consder a membrane whch separates two aqueous regons, whch are denoted nner and outer. At tme, t = 0, the nner regon contans a concentraton, C 1, of (potassum) and Cl (chlorde) ons and the outer regon contans a concentraton C 2 of Na + (sodum) and Cl ons. For electrcal neutralty, C 1 = C 2. The membrane s permeable to and Cl, but mpermeable to Na +. At tme, t = 0 + : concentraton gradent INNER Cl + E-feld OUTER concentraton gradent Cl Cl net movement wll dffuse through the membrane, along ts concentraton gradent; ths gves rse to the, E. The E-feld causes Cl to move along ts to the outer regon. The movement of s opposed by the E-feld and the movement of Cl s opposed by ts concentraton gradent.. There s a net movement of and Cl from the nner to the outer regon. At some tme, t = t eq the system wll reach ts equlbrum state. The concentraton gradent drvng from the nner to the outer regon s balanced by the E-feld. In turn, the potental gradent drvng Cl from the nner to the outer regon s offset by the concentraton gradent of Cl. There s no net movement of ons and a measurable potental, called the transmembrane potental exsts across the membrane. concentraton gradent INNER - electronegatve wth respect to the outer regon Cl Cl concentraton gradent net movement OUTER 2

3 The transmembrane potental can be approxmated usng the Nernst equaton: RT K o E ln F K where: R = gas constant = 1.99 cal/mole/deg T = absolute temperature (K) F = faraday = cal/v/mole K o = concentraton of n the outer regon K = concentraton of n the nner regon RT At 25C: mv. In the squd gant axon 2 K = 400 mm and K o = 20 mm and the F Nernst equaton gves a value: E = 77 mv, whch s close to the measured value of the restng potental. The cell membrane s not completely mpermeable to Na + ons; the estmate of the restng potental gven by the Nernst equaton can be made more accurate by takng Na + and Cl nto account, usng the Goldman equaton: RT PK K 0 PNa Na0 PCl Cl E ln F PK K PNa Na PCl Clo where P K, P Na and P Cl are the membrane permeabltes to, Na + and Cl respectvely. At rest P K : P Na : P Cl s approxmately 1: 0.04: As we wll see later, the nstantaneous value of P K, P Na and P Cl depends on the membrane potental. Actve Transport of Na + and Ions Specalzed transmembrane protens are present n the cell membranes of actve cells (and many other types of cells). The functon of these protens s to move Na + out of the cell, aganst ts concentraton and s, and to move nto the cell, aganst ts concentraton gradent. Ths process s called the Na + / pump. Snce both Na + and are moved aganst ther gradents, energy s requred for the process. The Na + / pump uses ATP, whch s the energy molecule manufactured wthn cells. The Na + / pump s mportant for mantanng ntracellular and extracellular concentratons of Na + and and consequently the transmembrane potental. Because the membrane s not strctly mpermeable to Na + and (as noted above), some Na + ons wll dffuse nto the cell, down ther concentraton gradent. Ths ncreases the actng on and some ons move out of the cell. If ths were allowed to contnue over a long tme, the transmembrane potental would eventually run down. The sodum/potassum pump mantans a 10 tmes greater 2 The squd gant axon s a large nerve fbre or cell that ca be extracted from a squd. The fbre s up to 1 mm n dameter, whch s consderably larger than other nerve fbres. It s large sze permtted researchers to do a number of experments that otherwse would not have been possble. In a seres of experments usng squd gant axons, A.L. Hodgkn and A.F. Huxley elucdated the propertes of exctable cells and generaton of acton potentals. They receved the Nobel prze n Physology or Medcne n 1963 for ther work. 3

4 concentraton of Na + outsde the cell than nsde the cell and a 20 tmes greater concentraton of nsde the cell than that outsde the cell 3. Other Intracellular Charges There are a large varety of molecules nsde the cell. Of these, large proten molecules, whch are negatvely charged, contrbute to the electronegatve potental nsde the cell. The Acton Potental In the restng state, an exctable cell s sad to be polarzed and s electronegatve nsde wth respect to outsde. An njecton of postve charge nto the nteror of the cell wll cause the transmembrane potental to rse towards zero, whch s called depolarzaton. If a very small amount of charge s njected, the membrane wll become slghtly depolarzed n a small regon surroundng the stmulus pont; ths s due to electrotonc current spread n the membrane. Wth the removal of the current source, the membrane rapdly repolarzes. If, however, enough charge s njected to rase the transmembrane potental to a partcular value called the threshold value a process begns whereby the potental rses rapdly and reverses (the cell becomes electropostve nsde wth respect to outsde), and then rapdly repolarzes. Ths transent event s called the acton potental. The duraton of the acton potental s dependent on the propertes of the cell membrane and s generally on the order of 1-3 ms. Depolarzaton phase 55 mv Repolarzaton phase 0 t (ms) threshold -77 mv Transmembrane potental recorded after applcaton of a stmulatng current. An acton potental s produced when the current rases the transmembrane potental to the threshold level. An dentcal acton potental s produced each tme suffcent stmulus s appled to the membrane. Electrotonc potentals Postve after potental The Ionc Bass of the Acton Potental When an exctable cell has been depolarzed such that the membrane potental reaches threshold, the cell suddenly becomes very permeable to Na + (Na + permeablty wll ncrease 5000 tmes or more) and Na + ons rush down ther electrochemcal gradent nto the cell. Durng 3 See: 4

5 ths phase (the depolarzaton phase), Na + permeablty s much greater than permeablty and the membrane potental approaches the value of the Nernst potental for Na + : RT [ Nao ] 440 ENa ln 25.7ln 55.9 mv for the squd gant axon F [ Na ] 50 Wthn a few tenths of a ms after exctaton, the membrane reverts to beng relatvely mpermeable to Na + and the nrush of Na + stops. At ths pont, the membrane permeablty to has ncreased and leaves the cell, resultng n membrane repolarzaton. Permeablty to remans hgh for a few ms causng a postve after potental, where the membrane s more electronegatve, nsde wth respect to outsde, than at rest. Ths condton s termed hyperpolarzaton. Followng the postve after-potental, the membrane returns to ts restng state. conductance (ms/cm 2 ) Na + Change n membrane conductance to Na + and durng acton potental producton..01 t (ms) Propagaton of the Acton Potental When an acton potental has been elcted n a regon of a nerve or muscle cell, the potental wll propagate away from the pont of exctaton at a constant velocty n both drectons. An acton potental occurrng at any pont along the cell s an exact replca of the acton potental produced at the pont of exctaton. When a cell s excted, an actve regon, n whch the membrane potental reverses, forms. Ths creates local current flow along the surface of the membrane. Ths current flow results n depolarzaton of the adjacent regons of the membrane and subsequent producton of acton potentals n these regons. In ths way, the acton potental travels at a constant velocty along the cell, away from the pont of exctaton. Ths s llustrated n the fgure on the next page. The prevously actve regon of the cell s not re-excted due to a property of exctable cells called refractorness. For a short tme (approxmately 2 ms) followng the start of the acton potental, the cell membrane wll not respond to any stmulus, regardless of ntensty; ths s the absolute refractory perod. Ths perod generally corresponds to the duraton of the spke of the acton potental. For approxmately ms followng the absolute refractory perod, a stmulus of greater than normal ntensty s requred to elct a response and the ampltude of the resultant acton potental wll be reduced; ths s the relatve refractory perod. The requred stmulus ntensty gradually dmnshes untl a response can be evoked wth normal stmulus ntensty. 5

6 Actve regon Travelng wave front Propagaton of the acton potental along the exctable cell. When a cell s stmulated, an acton potental wll travel away from the pont of stmulaton at a constant velocty n both drectons. Prevously actve regon Cell-cell Communcaton Synaptc Transmsson Nerve cells communcate wth other nerve cells or wth muscle cells va specalzed junctons called synapses. The communcatng cell s called the pre-synaptc cell and the cell recevng the communcaton s called the post-synaptc cell. A nerve cell wll have multple (sometmes hundreds or thousands) synaptc contacts on ts dendrtes and cell body. These synapses can be exctatory or nhbtory. A sngle exctatory synaptc potental wll not result n an acton potental n a post-synaptc nerve cell. Instead, the synaptc potentals summate spatally and temporally to alter the cell s transmembrane potental; f the transmembrane potental reaches threshold, an acton potental wll then occur. A muscle cell receves a sngle synaptc nput from a termnal branch of a motor neuron; a nerve-muscle synapse s called a neuromuscular juncton. A sgnal receved at a neuromuscular juncton s strctly exctatory and wll result n producton of an acton potental n the post-synaptc muscle cell. Anatomy of the synapse The end of each axon termnal branch s enlarged to form a structure called a termnal button; ths s located a very short dstance (30-50 nm) from the post-synaptc cell membrane. The gap between the termnal button and the post-synaptc cell s called the synaptc cleft. In the termnal button are many vescles small, membrane-enclose packets flled wth specalzed molecules called neurotransmtters. When an acton potental arrves at the termnal button, neurotransmtter molecules are released nto the synaptc cleft and dffuse across to the postsynaptc membrane, where they attach to specalzed receptors, causng the post-synaptc membrane to depolarze (exctatory synapse) or hyperpolarze (nbtory synapse). 6

7 Termnal button of the motor nerve Vescles contanng neurotransmtter (acetylcholne) Post-synaptc membrane wth specalzed receptors Synaptc transmsson at a neuromuscular juncton: 1. An acton potental arrves at the termnal button of the motor nerve 2. Vescles release the neurotransmtter, acetylcholne (ACh), nto the synaptc cleft 3. ACh molecules dffuse across the cleft to the post-synaptc membrane and attach to specalzed receptors, rasng the membrane s permeablty to Na + 4. The post-synaptc membrane depolarzes and an acton potental s generated at the neuromuscular juncton 5. The acton potental wll travel away from the neuromuscular juncton n both drectons at a constant velocty 6. ACh s broken down by cholnesterase n the synaptc cleft and taken back nto the presynaptc cell References Brnley, F.J. Exctaton and conducton n nerve fbres, n V.B. Mountcastle (ed.) Medcal Physology, 14 th ed., Mosby, St. Lous, pp , Katz, B. Nerve, Muscle and Synapse, McGraw-Hll, NY, Malmvuo, J. and Plonsey, R. Boelectromagnetsm: Prncples and Applcatons of Boelectrc and Bomagnetc Felds, Oxford U. Press, New York, Ncholls, J.G. From Neuron to Bran, 4 th ed.. Snauer Assocates, Sunderland, Mass, Web Resources: W. Gerstner and W.M. Kstler, Spkng Neuron Models, Cambrdge Unversty Press, Flm clps of experments wth the gan squd axon can be vewed at: Clck on the lnk: Vdeos on "The Squd and ts Gant Nerve Fber. You need Quck Tme player to vew these clps. 7