Bioelectrical Signaling PDF

BIOELECTRICAL SIGNALING Danny M. Pincivero, Ph.D. 1 Nerves 2  Plasma membranes CHARACTERISTICS 1) Forms sheet-like structures Forms a closed boundary….. 2 layers thick (60 – 100 Å)…... 2) Consists mainly of lipids and proteins...

BIOELECTRICAL SIGNALING Danny M. Pincivero, Ph.D. 1 Nerves 2  Plasma membranes CHARACTERISTICS 1) Forms sheet-like structures Forms a closed boundary….. 2 layers thick (60 – 100 Å)…... 2) Consists mainly of lipids and proteins 1:4 to 4:1 ratio…... Mitochondria…... Plasma membrane…... Some membranes contain carbohydrates….. 3) Hydrophilic and hydrophobic Spontaneous formation of. Barrier to the flow of polar molecules. 4) Protein-function specificity Channels, pumps, energy transducers, receptors. 3  Plasma membranes 5) Polarized structures Inside of cell is typically electronegative….. Approximately –60 mV. 6) Fluid structures “Two dimensional solutions of oriented proteins and lipids” Lipid molecules: diffuse rapidly through membrane in the plane Lipids and proteins do not 4  Plasma membranes FLUID MOSAIC MODEL Membranes are not rigid…... Membrane protein features Transport/attachment….. Signal transduction…... Larger than lipids….. Immobile proteins…... 5  Plasma membranes Receptors Channel Cell identity Enzymes Gated channel CAMs 6  Plasma membrane STRUCTURE Thin film of lipid and protein molecules Dynamic, fluid structure 7  Membrane proteins 4 basic functions Transport Enzyme activity Signal transduction Attachment/recognition Integral membrane proteins (transmembrane) Hydrophobic, non-polar amino acids…… Hydrophilic, polar amino acids….. Peripheral membrane proteins Do not interact with hydrophobic core of membranes. Held to membrane surface……. E.g., cytoskeleton……. 8 Molecular Gradients Across Cell Membrane Figure 4-1 9  Plasma membranes Membrane permeability (P) – net rate of diffusion of a given substance through each unit area of the membrane for a unit [ ] difference on either side. Factors affecting membrane permeability: 1) Membrane thickness. 2) Lipid solubility. 3) Number of protein channels Increased rate of transport with greater channel density 4) Temperature. 5) Molecular weight of diffusing substance V =. 1 V= W 10 Exocytosis FUNCTIONS 1) Membrane components 2) Recycle endocytosis products. 3) Secretion Interior to exterior WBC……. Neurons…. Mucus….. 11  Neuromuscular junction Secondary synaptic cleft Vesicles Terminal axon Primary synaptic cleft Muscle fibre Myofibril J. Heuser & L. Evans, UCSF 12  Active transport Refers to moving an ion “uphill”. Requires “energy”: (a) metabolic (ATP), or (b) ion gradient. Resembles enzyme-substrate interactions……. Some ARE enzymes…… Characteristics 1) Substrate –. 2) Binding site on transporter – 3) Specific affinity – 4) Presence of competitive and non-competitive inhibitors. 13  Active transport Types of transporters 1) Uniporter – transports only 1 solute (molecule or ion) 2) Symporter (co-transporter) – transport of 1 solute COUPLED to the transport of a SECOND solute…... 3) Antiporter (exchanger) – transport of 1 solute COUPLED to the transport of a SECOND solute….. Primary active transport Harnesses stored chemical energy…….. ATP used DIRECTLY to move ions…… Na+/K+ ATPase Secondary active transport Uses stored chemical energy……. Harnesses stored electrochemical gradient energy. 14  ATP-driven “pumps” 1) P-type pumps SERCA Phosphorylate themselves during cycle Ion pumps…… Spends $$ Primary active transport. SarcoEndoplasmic Reticulum Ca++ ATPase. Bublitz et al, PLoS ONE, 13(1):e0188620, 2018. 15  ATP-driven “pumps” Oxidative phosphorylation 2) F-type pumps Turbine-like proteins…. Bacteria (plasma membrane) Mitochondrion (inner membrane) Makes $$ 16  Cell membranes Membrane potential Refers to the electrical energy separation (difference) across the cell membrane……sets up the “potential” to do physical work (i.e., moving ions across the membrane)……. If the membrane potential is 0 mV, you have an equal “amount” of electrical charge on both sides of the membrane. Equilibrium Combination of electrical and concentration gradients. Even balance of ions with no NET movement. Key points: 1) Small change in ion concentration induces large changes in membrane potential. 2) The difference in electrical charges are close to the membrane. 3) The balance of ions is maintained by active “pumps”. 17  Bioelectrical signaling Mechanism Gated channels……. Facilitated transport……. Proteins contain…... Gates……. 3 TYPES OF ION CHANNELS Voltage-gated. Electrical environment determines. Ligand-gated. A ligand (molecule) binds to the ion channel. Binding opens or closes the gate……. Mechanically-gated. “Stretch” receptors. Requires application of……. 18  Element 11 – Sodium (Na) e- e- e- e- e- 11+ e- 11 n e- e- e- e- e- 19  Ion distribution Skeletal muscle fibres Ion Extracellular Intracellular [Ion]O EN Concentration Concentration [Ion]I (mM) (mM) (mV) Na+ 145 12 12 +67 K+ 4 155 0.026 -98 Ca++ 1.5 100 nM 15,000 +129 Cl- 123 4.2 29 -90 EN calculated for individual ions TABLE 2.1 Extracellular and Intracellular Ion Concentrations and Resultant Equilibrium Potentials Concentration (mM) Equilibrium Potential (mV) Ion Intracellular Extracellular Squid neuron Potassium (K+) 400 20 –75 Sodium (Na+) 50 440 +55 Chloride (Cl−) 110 560 –41 Calcium (Ca2+) 0.0001 10 +145 Mammalian neuron Potassium (K+) 140 5 –88 Sodium (Na+) 12 145 +66 Chloride (Cl−) 8 110 –69 Calcium (Ca2+) 0.0001 1.2 +124  Resting membrane potential Electrical charge separation across a membrane…….. Neuron?........ Muscle cell?...... RMP = -80 to -60 mV (depends on the cell)…….. Cytosol vs extracellular fluid. DEpolarization? Cell is no longer “polarized”……how?. REpolarization……. HYPERpolarization…….. 2 types of biological signals……. 22  Cell membranes Nernst equation: Is a measure of the equilibrium potential for ion, S. Walther Hermann Nernst June 25, 1864 – November 18, 1941 Nobel Prize (Chemistry), 1920 “in recognition for his work in thermochemistry” RT [ S ]2 EN = ln zSF [ S ]1 http://www.nobelprize.org/nobel_prizes /chemistry/laureates/1920/nernst- facts.html R = constant (8.3145 J·mol-1·K-1) Z = charge on the atom, S (valence) F = Faraday’s constant (9.6485 x 104 C·mol-1) EN = voltage difference across a membrane to hold that ion in equilibrium 23  Cell membranes Nernst equation: Example, Na+ RT [ Na]o ENa + = ln F [ Na]i o = outside cell i = inside cell RT/F = 26.73 mV. (at 37 deg C) [Na]o = 145 mM [Na]i = 12 mM Calculate ENa 24  Nernst equilibrium ENa = +67 mV. EK = -98 mV. What do these values mean? To hold sodium in equilibrium concentrations (145 mM outside and 12 mM inside), need a voltage difference of +67 mV on the INSIDE of the cell. KEY CONCEPT: opposite charges attract, like charges repel (polarity). What is the effect of a positive voltage inside the cell on Na+? What is the effect of a negative voltage inside the cell on K+? What exists for a muscle cell? 25  Cell membranes RMP (resting membrane potential): What exists in a skeletal muscle cell?...... -65 mV. RT PK[ K ]o + PNa[ Na]o + PCl[Cl ]i EREV = ln F PK[ K ]i + PNa[ Na]i + PCl[Cl ]o EREV = reversal potential (zero current potential) Weighted mean of all ion effects P = permeability of cell to that ion PK+ /PNa+ = 0.086 (sodium channel) PH+ /PNa+ = 252 (sodium channel) PNa+ /PK+ =