BME 502 / handout #2 BME 502 -- Handout #2 Passive Membrane Properties all of the ligand, voltage, and ion-sensitive conductances flow through the cell membrane, which has two important properties that determine the consequences of the current flow: membrane resistance and capacitance consider resistance first membrane resistance i. membrane resistance consists of both rm (membrane resistance) and ri (internal resistance) ii. ri increases with distance: for all patches in membrane, rm is equivalent but for any one patch of membrane, ri 's sum with distance iii. thus, will be less current to flow through rm for patches of membrane farther from a point of 1 BME 502 / handout #2 current injection 2 BME 502 / handout #2 precise relation between amplitude and distance given by: Install Equation Editor and doubleclick here to view equation. where V0 is the membrane potential at point zero, Vx is the membrane potential at point x, and λ = space constant, or distance at which Vx decrements to 1/3 of original value units: λ is a distance, in cm; x is a distance, in cm Vx and V0 both in volts functional consequence: spatial summation V0 is proportional to the size of the injected current, because Install Equation Editor and doubleclick here to view equation. rinput is the input resistance, or the average resistance presented by the membrane to the flow of current along the axoplasm and back out through the membrane 3 BME 502 / handout #2 so the two parameters, rinput and λ determine the shape of the curve of membrane potential produced in response to an injection of current: r input determines the height of the potential at the point of injection, and λ determines the lateral spread, i.e., the rate of decay as a function of distance 4 BME 502 / handout #2 rinput and λ depend on both rm and ri relation between λ and membrane resistance: Install Equation Editor and doubleclick here to view equation. interpretation: λ, the distance over which the potential change spreads increases with increases in membrane resistance (which prevents loss of current across the membrane) and decreases with increasing internal resistance (which resists current flow along the core of the fiber) these parameters are influenced by morphology of neuron: rm inversely proportional to surface area (# of channels) surface area of a cylinder = 2 π a l as surface area of cell , (diameter ), rm , so λ also ri inversely proportional to cell volume volume of cylinder = π a2 l as cell size , volume in proportion to square of diameter, so ri disproportionately more than rm , so that λ as cell size increases bottom line: larger cells will have a higher length constant than smaller cells likewise, rinput depends on both rm and ri: Install Equation Editor and doubleclick here to view equation. 5 BME 502 / handout #2 rm and ri are always specified for a cylindrical segment of axon, 1-cm in length the dimensions of ri are ohm/cm because the resistance along the membrane increases as length increases the dimensions of rm are Ω-cm because the resistance through the membrane decreases as length increases (more channels for current to flow through); so rm must be inversely proportional to length, so Ω-cm / cm = Ω these parameters provide information about the resistive characteristics of a cylindrical segment of axon, 1-cm in length do not provide information about the specific resistivities of the membrane or the cytoplasm because they depend on the size of the neural process (dendrite or axon) for example, all other things being equal, would expect a 1-cm length of small diameter fiber to have a higher membrane resistance than a larger diameter fiber of the same constituent membrane, because the smaller diameter fiber has less membrane surface, and thus would have fewer channels if the radius, a, is known, then can determine the specific resistance of the membrane and the cytoplasm the specific membrane resistance, Rm, is defined as the resistance of 1 cm2 of membrane is independent of geometry, and thus allows comparison of membranes membrane resistance as circumference Install Equation Editor and doubleclick here to view equation. Install Equation Editor and doubleclick here to view equation. where a is the radius units: rm in ohm-cm, a in cm, Rm in ohm-cm2 6 BME 502 / handout #2 specific resistance of the axoplasm, R i, is the internal longitudinal resistance of a 1-cm length of axon 1 cm2 in cross-sectional area also independent of geometry, and gives a measure of how freely ions move through the intracellular space because ri increases as cross-sectional area decreases: Install Equation Editor and doubleclick here to view equation. Install Equation Editor and doubleclick here to view equation. units: ohm-cm thus, input resistance also depends on geometry: Install Equation Editor and doubleclick here to view equation. 7 BME 502 / handout #2 membrane capacitance cell membrane also can store charge, so acts as capacitor capacitor consists of two conducting surfaces separated by a layer of non-conducting, or insulating, material capacitance, C, is defined as the amount of charge, Q, it will accumulate for each volt of potential, V, applied to it: Install Equation Editor and doubleclick here to view equation. Install Equation Editor and doubleclick here to view equation. capacitance has units of coulombs per volt, or farads, F Install Equation Editor and doubleclick here to view equation. capacitance proportional to membrane surface area, because greater change in Ic required for a given change in voltage and inversely proportional to membrane thickness (decreased capability for storing charge) because cell membranes are on the order of 7nm, capable of storing relatively large amount of charge; cell membranes typically have a capacitance on the order of 1μF/cm2 functional consequence of capacitance: considering original RC membrane circuit, a. b. c. d. driving force = battery (polarity in figure is arbitrary) membrane resistance, rm = reciprocal of conductance ri, internal resistance Cm, membrane capacitance 8 BME 502 / handout #2 current injected into cell initially flows to charge the capacitance of the membrane (because sees the capacitor as a zero resistance) changes Vm at that local part of membrane any change in Vm for the capacitor must be matched by a change in Vm for the resistive part of the membrane as ΔVm increases, ionic current across the resistance also increases since Im = Ii + Ic , Ic decreases as ΔVm and Ii increase relationship expressed by: Install Equation Editor and doubleclick here to view equation. or, Install Equation Editor and doubleclick here to view equation. where V0= the voltage at time 0, at the beginning of the injection of current Vt = the voltage at time t t = the time from the beginning of the injection of current τ = membrane time constant where τ = RC where R = rm and represents time to increase charge to 2/3 of asymptotic Vm 9 BME 502 / handout #2 time to decrease to 1/e from initial voltage, V0 : Install Equation Editor and doubleclick here to view equation. consequence: alters the time course of the transmembrane voltage 10 BME 502 / handout #2 11 BME 502 / handout #2 consequence: temporal summation 12 BME 502 / handout #2 because of multiple capacitances in successive patches of membrane, time constant is not constant, but varies according to distance: at point of current injection, Vm rises to 84% of maximum within 1 time constant at 1 length constant distance, V m rises to 63% of maximum, i.e., τ accurate at 2 length constants distance, V m rises to 35% of maximum within 1 time constant so how to measure τ accurately ? must measure Vm at a site other than the site of current injection must know the distance between site of current injection and site of measurement the three parameters of rin, λ, and τ provide all of the information necessary to predict the evolution of membrane potential changes in response to a current injection provided the geometrical properties of the axon / dendrite / soma are known assuming only membrane exhibits only passive properties, i.e., no voltage-dependent or ion-sensitive conductances same principles apply to case when hyperpolarizing current is injected 13