BIO 3350 Neurobiology Past Lecture Notes (Winter 2025)

BIO 3350 Principle of Neurobiology Winter 2025 Neuronal excitability Jean-Claude Béïque [email protected] Outline: - Ionic bases of neuronal excitability - Ionic flow through channels - Ionic basis of the resting membrane potential  Scales of neural...

BIO 3350 Principle of Neurobiology Winter 2025 Neuronal excitability Jean-Claude Béïque [email protected] Outline: - Ionic bases of neuronal excitability - Ionic flow through channels - Ionic basis of the resting membrane potential  Scales of neural organization http://parkinsonhope.org/wp-content/uploads/2013/07/FEAT-DTI-is.jpg Microscale Mesoscale Macroscale Neurons are input-output Machines Connectivity Dendrite (map) Transformation (How?) Axon Neural code (What?) The Cast of Chemicals Cytosolic and Extracellular Fluid – Water Key ingredient in intracellular and extracellular fluid Key feature – water is a polar solvent Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins The Cast of Chemicals Cytosolic and Extracellular Fluid (Cont’d) – Ions: Atoms or molecules with a net electrical charge Cations: positive charge Anions: negative charge Spheres of hydration Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins The Cast of Chemicals The Phospholipid Membrane – The Phospholipid Bilayer Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins The Cast of Chemicals Protein – Channel Proteins Polar R groups and nonpolar R groups Ion selectivity and gating Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins  The Movement of Ions Diffusion – Dissolved ions distribute evenly – Ions flow down concentration gradient when: Channels permeable to specific ions Concentration gradient across the membrane  Electricity – Electrical current flow across a membrane – Ohm’s law V=IR or I = gV – Electrical conductance (g) and resistance (R); R = 1/g Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins File:WholeCellPatchClamp-03.jpg  The Ionic Basis of The Resting Membrane Potential The Distribution of Ions Across The Membrane – K+ more concentrated on inside, Na+ and Ca2+ more concentrated outside The Ionic Basis of The Resting Membrane Potential Equilibrium Potentials (Cont’d) – 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 © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins  The Ionic Basis of The Resting Membrane Potential E= The membrane potential (in volts, equivalent to joules per coulomb) R= The ideal gas constant (joules per kelvin per mole) T= The temperature in kelvin F= Faraday's constant (coulombs per mole) The Ionic Basis of The Resting Membrane Potential The sodium-potassium pump – Enzyme - breaks down ATP when Na present – Calcium pump: Actively transports Ca2+ out of cytosol Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins The Ionic Basis of The Resting Membrane Potential Vm=0 Equilibrium Potential (Eion) – No net movement of ions when separated by a phospholipid membrane – Equilibrium reached when K+ channels inserted into the phospholipid bilayer – Electrical potential difference that exactly balances ionic Vm=-80 concentration gradient Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins The Ionic Basis of The Resting Membrane Potential Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins 1) V=IR 2) I=1/R x V 3) I=g x V 4) Say for a K conductance, IK=gK x (Vm-EK) The Ionic Basis of The Resting Membrane Potential Equilibrium Potentials (Cont’d) – Four important points Large changes in Vm 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 Concentration difference known: Equilibrium potential can be calculated Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins The Ionic Basis of The Resting Membrane Potential Relative Ion Permeabilities of the Membrane at Rest – Selective permeability of potassium channels - key determinant in resting membrane potential – Many types of Potassium Channel Lily & Yuh Nung Jan—amino acid sequences; Family of K+ channels e.g., Shaker Potassium Channel Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins The Ionic Basis of The Resting Membrane Potential Relative Ion Permeabilities of the Membrane at Rest – K+ channels: 4 subunits – Channel selectively permeable to K+ ions – MacKinnon—2003 Nobel Prize Mutations of specific K+ channels; Inherited neurological disorders Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins The Ionic Basis of The Resting Membrane Potential Relative Ion Permeabilities of the Membrane at Rest – Regulating the External Potassium Concentration Blood-Brain barrier Potassium spatial buffering Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins Concluding Remarks Activity of the sodium- potassium pump Large K+ concentration gradient Electrical potential difference across the membrane – Similar to a battery Potassium channels – Contribute to resting potential Roles of ion pumps Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins