Remember James ..1. The doctor noticed pigment deposits (bone spicule pattern) in the periphery of James’retina.2. Abnormalities were noticed in a follow-up electroretinogram test.3. The doctor thinks James has a degree of night blindness as well as defective peripheral visionThe a wave signifies, in part, the activity of photoreceptorsThe b wave reflects activity of inner retina ( eg bipolar and Muller cells)Compare a typical cellQuickTime™ and a decompressorare needed to see this picture. .to a rod photoreceptorThe plasma membrane is the barrier between cytoplasm and extracellular space - ion concentrations are different on the two sides.In all cells there is an electrical voltage (potential difference) across the plasma membrane.Resting Membrane PotentialBaseline electrical condition(of ALL cells)Depends on 2 parametersA. Transmembrane IonGradients (particularly Na+& K+)B. Membrane Permeabilityto those ionsA-= negatively charged protein and phosphateA. Ion GradientsNa,K-ATPase develops andmaintains steady-state iongradients for ALL cellsNa+Na+K+K+B. PermeabilityATPK+channels present in ALL cellsNa+Na+K+K+ATP(+)(-)cyto outChannelCytoplasm Outside2 opposing forcesChemical & Electrical1) Chemical force (K+gradient)Tends to ‘push’ K+out2) Developed Electrical Force(inside negative)Tends to ‘pull’ K+inNa+Na+K+K+ATP(+)(-)K+channelcytoplasmoutsideIn most cells the chemical and electrical forces for K+are nearly in balanceWhat does that mean to us?The outwardly-directed K+gradientresults in an inside-negativeelectricalpotentialThe ‘electrical potential difference’ (PD)is measured in units of millivolts (mV)The typical value is -50 to -100 (mV)An inside-negative PD, determined mostly by K+, is a characteristic of cells in their resting state.III. Modulation of the PDChanges in ‘Membrane Permeability’can produce large changes in the‘Membrane Potential’Na+Na+K+K+ATP(+)cyto outNa+Na+K+K+ATP(-)cyto outNa+Na+K+K+ATP(+)cyto outNa+Na+K+K+ATP(-)cyto outat Equilibrium:at Equilibrium:Electrical Force = Chemical ForceElectrical Force = Chemical Force(electrical (electrical ‘‘voltagevoltage’’= chemical = chemical ‘‘gradientgradient’’))VKzKF = RT ln[K+]in[K+]outVK= ln[K+]in[K+]outRTzKFNernst EquationNernst EquationWalther Nernst1920 Nobel Prizein ChemistryR = 8.31 J/(moldeg)T = 310oKz = valence (charge) = 1 for K+F= 96,500 coulombs/moleVK= ln[K+]in[K+]outRTzKFTo convert natural log (ln) tobase 10 log (log), multiply by 2.303VK= ln[K+]in[K+]outRTzKFVK log[K+]in[K+]out60 mVzKVK 60 mVVK 60 mVIf [KIf [K++]]inin= 100 mM and [K= 100 mM and [K++]]outout= 10 mM= 10 mMPrinciple:Principle:There are two driving forcesThere are two driving forceschemical force and electrical forcechemical force and electrical forceFor a single ion the For a single ion the Nernst Nernst equationequationdescribes thedescribes thetheoretical balance between these forces.theoretical balance between these forces.The The Goldman equationGoldman equationreflects the realreflects the realsituation where:situation where:(a) ions and chloride are involved(a) ions and chloride are involved(b)(b)ionic ionic permeabilities permeabilities can changecan changePK[K+]out+ PNa[Na+]out+ PCl[Cl]inPK[K+]out+ PNa[Na+]out+ PCl[Cl]inVm 60 mV logPK[K+]in+ PNa[Na+]in+ PCl[Cl]outPK[K+]in+ PNa[Na+]in+ PCl[Cl]out‘Goldman Equation’Sir Alan Lloyd Hodgkin Sir Bernard KatzDavid E. Goldman2 parameters of Goldman eq:2 parameters of Goldman eq:Ion PermeabilitiesIon Permeabilitiesrapidly variablerapidly variableIon GradientsIon Gradients‘‘stablestable’’PK[K+]out+ PNa[Na+]out+ PCl[Cl]inPK[K+]out+ PNa[Na+]out+ PCl[Cl]inVm 60 mV logPK[K+]in+ PNa[Na+]in+ PCl[Cl]outPK[K+]in+ PNa[Na+]in+ PCl[Cl]out‘Goldman Equation’PK[K+]out+ PNa[Na+]out+ PCl[Cl]inPK[K+]out+ PNa[Na+]out+ PCl[Cl]inVm 60 mV logPK[K+]in+ PNa[Na+]in+ PCl[Cl]outPK[K+]in+ PNa[Na+]in+ PCl[Cl]out‘Goldman Equation’Consider the hypothetical case of a membranepermeable only to K...0000‘NernstFactors that influence Factors that influence membrane potentialmembrane potentialA. Concentration gradient of each ionA. Concentration gradient of each ionIon [in] [out] Ion [in] [out] VVeqeq((NernstNernst))NaNa++12 mM 140 mM +64 mV12 mM 140 mM +64 mVKK++135 4 135 4 9292ClCl4 116 4 116 8888PPii101099cm/seccm/sec101077cm/seccm/sec101088cm/seccm/secB. Membrane Permeability to each ionB. Membrane Permeability to each ionGoldman prediction of Vm= 84 mVPK[K+]out+ PNa[Na+]out+ PCl[Cl]inPK[K+]out+ PNa[Na+]out+ PCl[Cl]inVm 60 mV logPK[K+]in+ PNa[Na+]in+ PCl[Cl]outPK[K+]in+ PNa[Na+]in+ PCl[Cl]outVNaVNaVKVKVClVClVmVm‘boundaryconditions’+50050100Membrane Potential (mV)So, at So, at ‘‘restrest’’PPKKdominatesdominates3Na+ATP3Na+2K+2K+In large part, it reflects theIn large part, it reflects theconstitutive activity of aconstitutive activity of apopulation of K Channelspopulation of K ChannelsWhat is thebasis of ‘PK’?Regulation of channel-mediated ionpermeability allows cells to change voltage1. Establish & maintain Na+and K+gradients2. Vary the activity of specific ion channelsTwo parts to manipulation of PD:Sodium channels are open in the darkLight leads to closure of