The ins and outs of ions in the nervous system

The ins and outs of ions in the nervous system

Abakumov M.A.

Moscow, 2015

Russian National Research Medical University

Cell interactions in nervous system

Astrocytes – green Neurons – red

Cell interactions in nervous system

Neuron structure

Dendrites

Axon

Myelin Sheath

CellBody

Axon

Node ofRanvier

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

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+ + + + +

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+ ++ +

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-70mV

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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 gradient2) 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

Axon

Myelin Sheath

CellBody

Axon

Node ofRanvier

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

Cerebroside

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