Resting potential 777072 224843906 2008-07-10T17:48:08Z Lova Falk 3665380 /* Measuring resting potentials */ link has died The '''resting potential''' of a cell is the [[membrane potential]] that would be maintained if there were no [[action potential]]s (no voltage-gated channels), [[Inhibitory Post-Synaptic Current|synaptic potential]]s, or other active changes in the membrane potential. In most neurons the resting potential has a negative value of ~-70mV, which by convention means that there is excess negative charge inside compared to outside. The resting potential is mostly determined by the concentrations of the [[ion]]s in the fluids on both sides of the [[cell membrane]] and the [[membrane transport|ion transport]] [[protein]]s that are in the cell membrane. How the concentrations of ions and the membrane transport proteins influence the value of the resting potential is outlined below. == Membrane transport proteins == For determination of membrane potentials, the two most important types of membrane ion transport proteins are [[ion channel]]s and [[ion pump|ion pumps]]. Ion channel proteins create paths across cell membranes through which ions can passively [[diffusion|diffuse]] without expenditure of energy. They have selectivity for certain ions, thus, there are [[potassium channel|potassium-]], chloride-, and [[Sodium ion channel|sodium-selective ion channels]]. Different cells and even different parts of one cell ([[dendrite]]s, [[cell body|cell bodies]], [[Node of Ranvier|nodes of Ranvier]]) will have different amounts of various ion transport proteins. Typically, the amount of certain potassium channels is most important for control of the resting potential (see below). Some ion pumps such as the [[Na+/K+-ATPase]] are electrogenic, that is, they produce charge imbalance across the cell membrane and can also contribute directly to the membrane potential. All pumps use energy to function. == Equilibrium potentials == For most animal cells [[potassium]] ions (K<sup>+</sup>) are the most important for the resting potential<ref name="squid">An [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Search&db=books&doptcmdl=GenBookHL&term=resting+potential+AND+neurosci%5Bbook%5D+AND+231082%5Buid%5D&rid=neurosci.figgrp.146 example] of an [[electrophysiology|electrophysiological]] experiment to demonstrate the importance of K<sup>+</sup> for the resting potential. The dependence of the resting potential on the extracellular concentration of K<sup>+</sup> is shown in Figure 2.6 of '''Neuroscience''', 2nd edition, by Dale Purves, George J. Augustine, David Fitzpatrick, Lawrence C. Katz, Anthony-Samuel LaMantia, James O. McNamara, S. Mark Williams. Sunderland (MA): Sinauer Associates, Inc.; 2001.</ref>. Due to the [[active transport]] of potassium ions, the concentration of potassium is higher inside cells than outside. Most cells have potassium-selective ion channel proteins that remain open all the time. There will be net movement of positively-charged potassium ions through these potassium channels with a resulting accumulation of excess positive charge outside of the cell. The outward movement of positively-charged potassium ions is due to random molecular motion ([[diffusion]]) and continues until enough excess positive charge accumulates outside the cell to form a membrane potential which can balance the difference in concentration of potassium between inside and outside the cell. "Balance" means that the electrical force ([[electric field|potential]]) that results from the build-up of ionic [[charge]], and which impedes outward diffusion, increases until it is equal in magnitude but opposite in direction to the tendency for outward diffusive movement of potassium. This balance point is an ''[[equilibrium potential]]'' as the net transmembrane flux (or [[electrical current|current]]) of K<sup>+</sup> is zero. The equilibrium potential for a given ion depends only upon the concentrations on either side of the membrane and the temperature. It can be calculated using the [[Nernst equation]]: :<math> E_{eq,K^+} = \frac{RT}{zF} \ln \frac{[K^+]_{o}}{[K^+]_{i}} , </math> where *''E''<sub>eq,K<sup>+</sup></sub> is the equilibrium potential for potassium, measured in [[volt]]s *''R'' is the universal [[gas constant]], equal to 8.314 [[joule]]s·K<sup>-1</sup>·mol<sup>-1</sup> *''T'' is the [[absolute temperature]], measured in [[kelvin]]s (= K = degrees Celsius + 273.15) *''z'' is the number of [[elementary charge]]s of the ion in question involved in the reaction *''F'' is the [[Faraday constant]], equal to 96,485 [[coulomb]]s·mol<sup>-1</sup> or J·V<sup>-1</sup>·mol<sup>-1</sup> *[K<sup>+</sup>]<sub>o</sub> is the extracellular concentration of potassium, measured in [[Mole_%28unit%29|mol]]·m<sup>-3</sup> or mmol·l<sup>-1</sup> *[K<sup>+</sup>]<sub>i</sub> is likewise the intracellular concentration of potassium Potassium equilibrium potentials of around -80 millivolts (inside negative) are common. Differences are observed in different species, different tissues within the same animal, and the same tissues under different environmental conditions. Applying the Nernst Equation above, one may account for these differences by changes in relative K<sup>+</sup> concentration or differences in temperature. For common usage the Nernst equation is often given in a simplified form by assuming typical human body temperature (37 C), reducing the constants and switching to Log base 10. (The units used for concentration are unimportant as they will cancel out into a ratio). For Potassium at normal body temperature one may calculate the equilibrium potential in millivolts as: :<math> E_{eq,K^+} = 61.54 \log \frac{[K^+]_{o}}{[K^+]_{i}} , </math> Likewise the equilibrium potential for sodium (Na<sup>+</sup>) at normal human body temperature is calculated using the same simplified constant. For chloride ions (Cl<sup>-</sup>) the sign of the constant must be reversed (-61.54 mV). If calculating the equilibrium potential for calcium (Ca<sup>2+</sup>) the 2+ charge halves the simplified constant to 30.77 mV. If working at room temperature, about 21 C, the calculated constants are approximately 58 mV for K<sup>+</sup> and Na<sup>+</sup>, -58 mV for Cl<sup>-</sup> and 29 mV for Ca<sup>2+</sup>. == Resting potentials == The resting membrane potential is not an equilibrium potential as it relies on the constant expenditure of energy (for [[ion pump|ionic pumps]] as mentioned above) for its maintenance. It is a dynamic diffusion potential that takes mechanism into account&mdash;wholly unlike the equilibrium potential, which is true no matter the nature of the system under consideration. The resting membrane potential is dominated by the ionic species in the system that has the greatest [[Electrical conductance|conductance]] across the membrane. For most cells this is potassium. As potassium is also the ion with the most negative equilibrium potential, usually the resting potential can be no more negative than the potassium equilibrium potential. The resting potential can be calculated with the [[Goldman equation|Goldman-Hodgkin-Katz voltage equation]] using the concentrations of ions as for the equilibrium potential while also including the relative [[semipermeable membrane|permeabilities]], or [[electrical conductance|conductances]], of each ionic species. Under normal conditions, it is safe to assume that only potassium, [[sodium]] (Na<sup>+</sup>) and [[chloride]] (Cl<sup>-</sup>) ions play large roles for the resting potential: <math>E_{m} = \frac{RT}{F} \ln{ \left( \frac{ P_{Na^+}[Na^+]_{o} + P_{K^+}[K^+]_{o} + P_{Cl^-}[Cl^-]_{i} }{ P_{Na^+}[Na^+]_{i} + P_{K^+}[K^+]_{i} + P_{Cl^-}[Cl^-]_{o} } \right) }</math> This equation resembles the Nernst equation, but has a term for each permeant ion. Also, ''z'' has been inserted into the equation, causing the intracellular and extracellular concentrations of Cl<sup>-</sup> to be reversed relative to K<sup>+</sup> and Na<sup>+</sup>, as chloride's negative charge is handled by inverting the fraction inside the logarithmic term. *''E''<sub>m</sub> is the membrane potential, measured in volts *''R'', ''T'', and ''F'' are as above *''P''<sub>X</sub> is the relative permeability of ion X in arbitrary units (e.g. [[Siemens_%28unit%29|siemens]] for electrical conductance) *[X]<sub>Y</sub> is the concentration of ion X in compartment Y as above. Another way to view the membrane potential is using the Millman equation: :<math>E_{m} = \frac{P_{K^+}E_{eq,K^+} + P_{Na^+}E_{eq,Na^+} + P_{Cl^-}E_{eq,Cl^-}} {P_{K^+}+P_{Na^+}+P_{Cl^-}}</math> or reformulated :<math>E_{m} = \frac{P_{K^+}} {P_{tot}} E_{eq,K^+} + \frac{P_{Na^+}} {P_{tot}} E_{eq,Na^+} + \frac{P_{Cl^-}} {P_{tot}} E_{eq,Cl^-}</math>, where ''P''<sub>tot</sub> is the combined permeability of all species, again in arbitrary units. The latter equation portrays the resting membrane potential as a ''[[weighted mean|weighted average]]'' of the reversal potentials of the system, where the weights are the relative permeabilites across the membranes (''P''<sub>X</sub>/''P''<sub>tot</sub>). During the action potential, these weights change. If the permeabilities of Na<sup>+</sup> and Cl<sup>-</sup> are zero, the membrane potential reduces to the Nernst potential for K<sup>+</sup> (as ''P''<sub>K<sup>+</sup></sub> = ''P''<sub>tot</sub>). Normally, under resting conditions ''P''<sub>Na+</sub> and ''P''<sub>Cl-</sub> are not zero, but they are much smaller than ''P''<sub>K+</sub>, which renders ''E''<sub>m</sub> close to ''E''<sub>eq,K+</sub>. Medical conditions such as [[hyperkalemia]] in which [[blood]] [[blood plasma|serum]] potassium (which governs [K<sup>+</sup>]<sub>o</sub>) is changed are very dangerous since they offset ''E''<sub>eq,K+</sub>, thus affecting ''E''<sub>m</sub>. This may cause [[arrhythmia]]s and [[cardiac arrest]]. The use of a [[Bolus (medicine)|bolus]] injection of potassium chloride in executions by [[Lethal_injection#Potassium_chloride|lethal injection]] stops the heart by shifting the resting potential to a more positive value, which depolarizes and contracts the cardiac cells permanently, not allowing the heart to [[repolarization|repolarize]] and thus enter [[diastole]] to be refilled with blood. == Measuring resting potentials == In some cells, the membrane potential is always changing (such as [[Cardiac pacemaker|cardiac pacemaker cells]]). For such cells there is never any “rest” and the “resting potential” is a theoretical concept. Other cells with little in the way of membrane transport functions that change with time have a resting membrane potential that can be measured by inserting an electrode into the cell<ref name="electrode">An illustrated example of measuring membrane potentials with electrodes is in Figure 2.1 of '''Neuroscience''' by Dale Purves, et al (see reference #1, above).</ref>. Transmembrane potentials can also be measured optically with dyes that change their optical properties according to the membrane potential. ==References== <div class="references-small"><references /></div> == See also== * [[Depolarization]] * [[hyperpolarization]] * [[membrane potential]] * [[action potential]] ==External links== *[http://www.ncbi.nlm.nih.gov/books/bv.fcgi?call=bv.View..ShowTOC&rid=neurosci.TOC&depth=2 Neuroscience] - online textbook by Purves, et al * [http://www.ncbi.nlm.nih.gov/books/bv.fcgi?call=bv.View..ShowTOC&rid=bnchm.TOC&depth=2 Basic Neurochemistry] Molecular, Cellular, and Medical Aspects by Siegel, et al * [[Bertil Hille]] ''Ion channels of excitable membranes'', 3rd ed., Sinauer Associates, Sunderland, MA (2001). ISBN 0-87893-321-2 * [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Citation&list_uids=15545342 Generation of resting membrane potential] Wright, S.H., ''Advances in Physiology Education'', '''28'''(1-4): 139-142, 2004, [[Category:Nervous system]] [[de:Ruhemembranpotential]] [[es:Potencial de reposo]] [[fr:Potentiel de repos]] [[pl:Potencjał spoczynkowy]] [[simple:Resting potential]] [[fi:Lepopotentiaali]] [[zh:静息电位]]