The ins and outs of ions in the nervous system Russian National Research Medical University The ins and outs of ions in the nervous system Abakumov M.A. Moscow, 2015

Cell interactions in nervous system

Cell interactions in nervous system Astrocytes – green Neurons – red

Neuron structure Dendrites Cell Body Axon Myelin Sheath Axon Node of Ranvier

Signal transduction through neurons Cells sustain transmembrane potential Positive charge is at the outer side of membrane Negative charge is at the inner side of the membrane Change in transmembrane potential counts as a current and creates nerve impulse

Signal transduction through neurons At resting state transmembrane potential is not changed and equal to -70mV At resting state no signal is transducted + - V -70mV

Signal transduction through neurons Transmembrane potential is sustained due to electrochemical gradient of K+ and Na+ ions Different concentration of K+ and Na+ ions is sustained by ATP dependent Sodium-Potassium Pump

Sodium-Potassium Pump Uses energy of 1 ATP to transport 3 Na+ out and 2 K+ inside of the cell. 70% energy consumed by neuron is required for this Runs anytime while not conducting an impulse Creates high [Na+] outside and high [K+] inside

Signal transduction through neurons. Membrane ion channels Transmembrane potential can be changed by opening of ion selective membrane channels Allow ion movement, thus changing transmembrane potential Specific to one type of ions

Membrane ion channels Passive Always open Provide free flow Active Open/close in response to external signal Ligand gated: Open in response to ligand binding Located on any cell membrane Voltage gated: Open/close in response to change in transmembrane potential Located on axolemma and sarcolemma Mechanically gated: opens after membrane distortion Located on sensory neurons for touch, pressure, vibration

Activatible sodium ion channel

Sodium selective ion channels Opening leads to Na+ flow into the cell Na+ flow favored by: 1) Chemical gradient 2) Electrical gradient Makes cell less negative This process is called depolarization Na+ equlibrium potential is +66 mV

Potassium selective ion channels Opening leads to K+ flow out of the cell K+ flow favored by chemical gradient Electrical gradient repels to K+ movement Makes cell more negative This process is called hyperpolarization K+ equlibrium potential is -90 mV

Ion transmembrane movement in signal transduction Open channel →ion flow→current→graded potential Graded potential is a localized shift in transmembrane potential due to movement of charges

Graded potential Occur on any membrane Can be depolarizing or hyperpolarizing Amount of depolarization depends on intense of external stimuli Passive spread from stimulation site by diffusion Effect decreases with distance from stimulation site Repolarization occurs as soon as stimuli is removed by leak channels and Na+/K+ pump

Action potential Occur on axolemma and sarcolemma Can be only depolarizing Starts only after threshold voltage (-55mV) is reached Effect for stimuli exceeding threshold will be the same (“all-or-none”) Passive spread from stimulation site by diffusion Action potential at one site depolarizes neighboring site Propagates through all membrane without decrease

Ion transmembrane movement in signal transduction

Ion transmembrane movement in signal transduction

Signal propagation through the axon Propagation is a transmission of action potential Continuous conduction - propagation of an action potential in a step-by-step depolarization of each adjacent area of an axon membrane Saltatory conduction - propagation of an action potential along exposed portions of a myelinated nerve fiber; "jumping" node to node

Continious propagation

Saltatory propagation

Neuron structure Dendrites Cell Body Axon Myelin Sheath Axon Node of Ranvier

Myelin and its structure

Myelin and its structure

Myelin and its structure.

Myelin and its structure. CNS.

Myelin and its structure. PNS.

Myelin composition. Water – 40% Dry mass: 1) Lipids (70-85%) 2) Proteins (30-15%) Typical lipid for myelin are cerebroside and sulfatide Typical proteins for myelin are myelin basic protein (MBP) and proteolipid protein (PLP) Other myelin specific proteins are: 2′:3′- cyclic nucleotide 3′-phosphodiesterase (CNP) and myelin-associated glycoprotein (MAG)

Myelin composition. Cerebroside and sulfatide

Myelin composition. Myelin basic protein (MBP) Highlu conserved gene Localized at cytoplasmic surface of major dense line. Stabilize major dense line by interacting with negatively charged phospholipids

Myelin composition. Proteolipid protein (PLP) Tetraspan transmembrane protein. Both N- and C-ends are on cytoplasmic site. Stabilizing intraperiod line of CNS myelin Determines membrane spacing

Myelin composition. Myelin-associated glycoprotein (MAG) Conytains single transmembrane domain Located on periaxonal glial membranes of myelin sheats Involved in interactions between glia and axons

Myelin composition. Compartmentalization.

Ion channels distribution in myelinated axon Sodium channels are located at the beginnig of axon and at the Ranvier nodes. Potassium channels are located under the myelin sheath closer to node of Ranvier