Physiology_Neuron_Memb (5).pdf

Nervous System : Cell Physiology Chapters 2, 6, 7, 8 and 10  The Neuron Doctrine: neurons are the elementary building blocks and signaling elements of the nervous system (Ramon y Cajal 1900s). Dendrites: Extensive branching, process synaptic inputs (4-5.000 - >100.000 Purkinje cells) C...

Nervous System : Cell Physiology Chapters 2, 6, 7, 8 and 10  The Neuron Doctrine: neurons are the elementary building blocks and signaling elements of the nervous system (Ramon y Cajal 1900s). Dendrites: Extensive branching, process synaptic inputs (4-5.000 - >100.000 Purkinje cells) Cell body (~50 μm): metabolic center +axon hillock. Axon: electrical signals over distances (0.1 mm to 2 m) to up to 1000 neurons (branches). Ramon y Cajal: -Neurons follow the principle of dynamic polarization, i.e. electrical signals are transmitted only in one way. -Neurons follow the principle of connectional specificity, i.e. neurons are not connected randomly, but in a specific way. dynamic polarization+ connectional specificity= modern connectionist approach to Neurosciences Ramon y Cajal: structure-function relationships What most distinguishes one type of neuron from another is form, specifically the number of the processes arising from the cell body.  Elecro-chemical properties of cells are important information Neuron 1 Neuron 2 Electrical (and chemical) signals Electrical signals? The most relevant is the difference in electrical potential between the interior of a neuron and the surrounding extracellular medium i.e. the membrane potential Neurons: membrane potential −70 mV Recording membrane potential (Vm) This is a reliable technique started to develop in late 1940s by Hodgkin, Huxley and Eccles. They won the Nobel prize in 1963. Glass micropipettes filled with concentrated salt solution serve as electrodes. Wires inserted into the back ends of the pipette and connected to a voltage amplifier and oscilloscope. Intracellular recording micropipettes are filled with a solution with similar ionic composition than intracellular environment. The diameter of the micropipette tip is small (< 1 μm) and can be inserted into the cell without damaging it. How the membrane potential is created? A neuron is like a bag of charged liquid! The neuron has a cell membrane, a lipid bilayer that is impermeable to ions like Na+, Cl-, K+, and Ca2+. There are ionic channels in the membrane that allow ions to enter or leave the cell. The net flux of ions depends on the electro-chemical gradients Electrical and chemical forces can counteract each other When the two forces are equal there is no net flux of the ion and the voltage difference across the membrane is called the equilibrium potential Equilibrium Potential (E) K+ -Specific for each ion Nernst Equation Eion=61/Z log(Cout/Cin) Cout : extracellular concentrazion of the ion Cin : intracellular concentrazion of the ion Z: valence of the ion 61: constant that is calculated from the gas costant R [8314.9 J/(kg mol K)] temperature T (on Kelvin’s scale: 273+ 37 oC) and Faraday’s costant F (the quantity of electricity contained in 1 mol of electrons: 96,484.6 C/mol of charge). EK+=61/+1 log(5/150)=-90mV  The bulk of the intracellular and extracellular fluids are neutral Vm is caused by a tiny excess of negative ions inside the cell and an excess of positive ions outside  What factors define the membrane resting potential Vm? 1) The electrogenic effect of the Na+/K+ pump (3 Na+ out / per 2 K+ in). 2) The asymmetric distribution of ions across the membrane Other ions: Mg+2,Ca+2, H+,HCO-3 Intracellular Extracellular Ionic Species Concentration Concentration Na+, K+, at large (but also Cl- ) determine Vm Sodium (Na+) 15 mM 145 mM Potassium (K+) 150 mM 4 mM Concentration gradients Calcium (Ca2+) 70 nM 2 mM (ion pumps e.g. Na+/ K+ ATPase) Hydrogen ion 63 nM (pH 7.2) 40 nM (pH 7.4) (proton, H+) Permeability Magnesium 0.5 mM 1 mM (Mg2+) Chloride (Cl−) 10 mM 110 mM Bicarbonate 15 mM 24 mM (HCO3−)  Equilibrium Potential (E) Na+ Nernst Equation for Sodium ENa+=61/+1 log(145/15)=+60mV The large part of neurons has a Vm near the EK+. This is because the membrane is more permeable to this ion compared to Na+ and Cl-.  Pumps and transporters regulate the chemical concentration gradients of Na+, K+, Ca2+, and Cl− ions. Moving ions and molecules against a concentration gradient Pump Na+ /K+ -ATPase trasports 3 Na+ ions outside the cell and 2 ions K+ inside and contributes to maintain the concentration gradient of Na+ and K+. Elettrogenic pump A blockade of the Na+/K+ pump will induce a 10 mV change in the membrane resting potential.  Ion channels: membrane proteins Proteins in membranes act as channels that allow specific ions to pass through. E.g. Pass K+ but not Cl- or Na+  Classification of ion channels Voltage-gated: Probability of opening depends on membrane voltage Chemically-gated: Binding to a chemical causes channel to open Mechanically-gated: Sensitive to pressure or stretch  Equivalent circuit of the neuronal membrane Ex -> trasmembranic electrochemical potential gx -> conductance (ion channels) Cm -> electrical capacitance (fosfolipidic bilayer) Membrane potential, Vm Of a cell that has a permeabililty for more than one ions Nernst Equazion + permeability (P) Goldman-Hodgkin-Katz Equation(GHK) 𝑷𝑲 𝑲𝒐𝒖𝒕 + 𝑷𝑵 𝑵𝒂𝒐𝒖𝒕 + 𝑷𝑪𝒍 𝑪𝒍𝒊𝒏 𝑽𝒎 = 𝟔𝟏𝒍𝒐𝒈 𝑷𝑲 𝑲𝒊𝒏 + 𝑷𝑵 𝑵𝒂𝒊𝒏 + 𝑷𝑪𝒍 𝑪𝒍𝒐𝒖𝒕 Permeability can vary a lot between different cell types Example: 𝑷𝑲 = 𝟏, 𝑷𝑵𝒂 = 𝟎. 𝟎𝟒, 𝑷𝑪𝒍 = 𝟎. 𝟒𝟓 𝟏(𝟓)+(𝟎.𝟎𝟒)(𝟏𝟒𝟓) +(𝟎.𝟒𝟓)(𝟕) 𝑽𝒎 = 𝟔𝟏𝒍𝒐𝒈 = −𝟕𝟎𝒎𝑽 𝟏(𝟏𝟓𝟎)+(𝟎.𝟎𝟒)(𝟏𝟓) +(𝟎.𝟒𝟓)(𝟏𝟎𝟎) How can the membrane potential be changed?  How can the membrane potential be changed? Graded potentials Graded potentials: Local changes in the membrane potential due to synaptic input from other neurons (via chemically-gated channels at synapses) Local changes cause the opening of voltage-gated channels=> depolarization or hyperpolarization of the dendrites. Action Potentials (spikes): the neurons’ output signal