Neuronal Science Lecture Notes PDF

신경과학원리 화 6교시, 목 4교시, 캠B146 정수영 교수 뇌∙인지과학부 Introduction • Action potential in the nervous system • Action potential vs. resting mem brane potential A simple reflex Copyright © 2016 Wolters Kluwer • All Rights Reserved The Cast of Chemicals • Cytosol and extracellular flu...

신경과학원리 화 6교시, 목 4교시, 캠B146 정수영 교수 뇌∙인지과학부 Introduction • Action potential in the nervous system • Action potential vs. resting mem brane potential A simple reflex Copyright © 2016 Wolters Kluwer • All Rights Reserved The Cast of Chemicals • Cytosol and extracellular fluid • Water • Key ingredient in intracellular and extracellular fluid • Key feature: Water is a polar solvent. Copyright © 2016 Wolters Kluwer • All Rights Reserved The Cast of Chemicals • Cytosolic and extracellular fluid • Ions: atoms or molecules with a net electri cal charge • Cations: net positive charge • Anions: net negative charge • Spheres of hydration Sodium chloride dissolved in water Copyright © 2016 Wolters Kluwer • All Rights Reserved The Cast of Chemicals • The phospholipid membrane • Hydrophilic compounds • Dissolve in water due to uneven electrical charge (e.g., salt) • Hydrophobic compounds • Do not dissolve in water due to even electrical charge (e.g., oil) • Lipids are hydrophobic. • Contribute to resting and action potentials Copyright © 2016 Wolters Kluwer • All Rights Reserved The Cast of Chemicals • The phospholipid bilayer Copyright © 2016 Wolters Kluwer • All Rights Reserved The Cast of Chemicals • Proteins • Molecules assembled from amino acids, composing: • Enzymes • Cytoskeletal elements • Receptors • Special proteins that span the phospholipid bilayer • Control resting and action potentials Copyright © 2016 Wolters Kluwer • All Rights Reserved The Cast of Chemicals • Protein structure • Amino acids • Alpha carbon and R groups Copyright © 2016 Wolters Kluwer • All Rights Reserved The Cast of Chemicals • Protein structure • Peptide bonds and polypeptides Copyright © 2016 Wolters Kluwer • All Rights Reserved The Cast of Chemicals • Protein structure • Four levels of protein structure • Primary • Secondary • Tertiary • Quaternary Copyright © 2016 Wolters Kluwer • All Rights Reserved Protein Structure Copyright © 2016 Wolters Kluwer • All Rights Reserved The Cast of Chemicals • Channel proteins • Polar R groups and nonpolar R groups • Ion selectivity and gating Membrane ion channel Copyright © 2016 Wolters Kluwer • All Rights Reserved The Cast of Chemicals • Ion pumps • Formed by membrane-spanning proteins • Use energy from ATP breakdown • Neuronal signaling Copyright © 2016 Wolters Kluwer • All Rights Reserved The Movement of Ions • Diffusion • Dissolved ions distribute evenly • Ions flow down concentration gradient when: • Channels are permeable to specific ions • Concentration gradient exists across the membrane Copyright © 2016 Wolters Kluwer • All Rights Reserved The Movements of Ions • Electricity • Electrical current influences ion movement. • Electrical conductance (g) and resistance (R) • R = 1/g • Electrical potential (voltage) Copyright © 2016 Wolters Kluwer • All Rights Reserved The Cast of Chemicals • Electrical current flow across a membrane • Ohm’s law I = gV Copyright © 2016 Wolters Kluwer • All Rights Reserved The Ionic Basis of the Resting Membrane Potential • Membrane potential: voltage across the neuronal membrane at any moment Copyright © 2016 Wolters Kluwer • All Rights Reserved The Ionic Basis of the Resting Membrane Potential • Equilibrium potential (Eion) • No net movement of ions when sepa rated by a phospholipid membrane • Equilibrium reached with K+ channel s in the phospholipid bilayer • Electrical potential difference that ex actly balances ionic concentration gra dient Copyright © 2016 Wolters Kluwer • All Rights Reserved The Ionic Basis of the Resting Membrane Potential • Equilibrium potential—(cont.) • Four important points • Large changes in Vm • From minuscule changes in ionic concentrations • Net difference in electrical charge • Inside and outside membrane surface • Rate of movement of ions across membrane • Proportional Vm – Eion • If concentration difference is known, equilibrium potential can be calculated. Copyright © 2016 Wolters Kluwer • All Rights Reserved Distribution of Electrical Charge Across the Membrane Copyright © 2016 Wolters Kluwer • All Rights Reserved The Ionic Basis of the Resting Membrane Potential • Equilibrium potential—(cont.) • Inside positively charged relative to outside Copyright © 2016 Wolters Kluwer • All Rights Reserved The Ionic Basis of the Resting Membrane Potential • Equilibrium potentials—(cont.) • The Nernst equation • Calculates the exact value of the equilibrium potential for each ion in mV • Takes into consideration: • Charge of the ion • Temperature • Ratio of the external and internal ion concentrations Copyright © 2016 Wolters Kluwer • All Rights Reserved The Ionic Basis of the Resting Membrane Potential • The distribution of ions across the membra ne • K+ more concentrated on inside, Na+ and Ca2+ more concentrated outside Copyright © 2016 Wolters Kluwer • All Rights Reserved The Ionic Basis of the Resting Membrane Potential • The sodium-potassium pump • An enzyme that breaks down ATP when Na present • Calcium pump actively transports Ca2+ out of cytosol. Copyright © 2016 Wolters Kluwer • All Rights Reserved The Ionic Basis of the Resting Membrane Potential • Relative ion permeabilities of the membrane at rest • Neuron membranes permeable to more than one type of ion. • Membrane permeability determines membrane potential. • Goldman equation • Takes into account permeability of membrane to different ions Copyright © 2016 Wolters Kluwer • All Rights Reserved The Ionic Basis of the Resting Membrane Potential • Relative ion permeabilities of the membrane at rest—(cont.) • Selective permeability of potassium channels—a key determinant of resting membrane potential • Many types of potassium channels • Lily & Yuh-Nung Jan: amino acid sequences, family of K+ channels • Example: Shaker potassium channel Copyright © 2016 Wolters Kluwer • All Rights Reserved The Ionic Basis of the Resting Membrane Potential • Relative ion permeabilities of the memb rane at rest—(cont.) • K+ channels: four subunits • Channel selectively permeable to K+ ions • MacKinnon—2003 Nobel Prize • Mutations of specific K+ channels; inherite d neurological disorders Copyright © 2016 Wolters Kluwer • All Rights Reserved A View of the Potassium Channel Pore Copyright © 2016 Wolters Kluwer • All Rights Reserved Copyright © 2016 Wolters Kluwer • All Rights Reserved The Ionic Basis of the Resting Membrane Potential • Importance of regulating external K+ concentration • Resting membrane potential is close to EK because it is mostly permeable to K+. • Membrane potential sensitive to extracellular K+ • Increased extracellular K+ depolarizes membrane. Copyright © 2016 Wolters Kluwer • All Rights Reserved The Ionic Basis of the Resting Membrane Potential • Relative ion permeabilities of the mem brane at rest—(cont.) • Mechanisms regulating the external potassi um concentration: • Blood-brain barrier • Potassium spatial buffering by astrocytes Copyright © 2016 Wolters Kluwer • All Rights Reserved Concluding Remarks • Activity of the sodium-potassium pump maintains large K+ concent ration gradient. • Electrical potential difference across the membrane is similar to a ba ttery. • Potassium channels contribute to resting potential. • Role of ion pumps Copyright © 2016 Wolters Kluwer • All Rights Reserved