Melvin Bae
2nd Faculty of medicine
2014
Basic principles


Ion flux; driven by force of diffusion and/
or electrostatic forces
Ions diffuse through channels ( „Leak
channels“ ) =constantly open
-> no further impuls needed

Gated channels

-> signal needed

Ion channels in each of living cell
Basic principles

Ions flow „downhill“ towards the concentration gradient
=CHANNEL

Ions flow „uphill“ against the concentrationgradient (energy needed)
= PUMP/TRANSPORTER

Membrane potential  via Goldman-Hodgkin-Katz equation (GHK equation)
(expansion of Nernst equation = only single Ion type)
Over 300 diferent ion channel types

Aprox.
107 ions / per second / per channel
Basic mechanisms
Silbernagl; Taschenatlas Physiologie
Main functions

1.) Ion concentraion sets up resting potential :
-
Na+ open  Depolarization
-
K+ open  Re- and Hyperpolarization
Main functions

2.) Volume Regulation and Salt balance:
-
Ion flux controles electrolyte distribution
-
Across epithel (basal labyrinth - typical)
-
Examples : gut, kidney, sweat glands or the choroid plexus.
Main functions

3.)
hormone secretion,
neurotransmitter release,
muscle contraction
Morphology of ion channels
Sodium channels

9 known in human being
(E.g. Neurons, myocites, glia cells )

big integral protein structure, ca 300kD,
aprox 0,3-0,5 nm diameter

Pore just big enough for 1 Na+ with one
associated H2O molecule
Compartements of a channel
- Ion conductiong pore
- Gate
- Sensor
Potassium Channels
Potassium Channels
1.
(Ion) Ligand gated (e.g. Ca++)
2.
Mechanical (e.g. tip links; stereocilia; inner hair cell -> ear )
3.
G Protein –(e.g. in cardiac muscle)
4.
(Metabolite) Ligand (e.g ATP reactive Beta cells)
-
Voltage gated K+ channels , only have open – closed state
-
( Na+ =O/C/I)
Blockers
-> Tetraethylamoniom closes K+ Channels ;
-> further more over 40 peptides from scorpion toxins;
-> Apamin (Toxin of bees)
Potassium Channels

Example of Potassium-channel regulated hormone
secretion in the Beta Cells in the Langerhans islands
(pancreas)
Resting potential
Necessary to maintain the electrochemical gradient : pumps and transporters
Patch clamp method

Refinement of voltage clamp method by Hodgkin and Huxley –
nobel price (1952)

Possible to measure selectively the Ion current through channels

Hollow end pipette 0,3-3 micrometer -> small membrane area
selcected/torn out and isolated

Similar to the programm which we had in class !!
Experiments with channel blocking drugs:

-> Tetradotoxin = blocks Na channels

-> Tetrathylammonium = blocks K Channels
Patch clamp method
Calcium channels
e.g. In Cardiac and smooth muscle cells, Presynpatic terminals etc.
Flux inside the cell/ to ER
Ca2+ (free)
EC= 2.5 mmol/L
IC = 0.1 micromol/L
5 types of Voltage gated
Ca2+ channels
Type
L – Type
(Long-lasting)
High
Voltage
Skelettal muscle,
smooth muscle,
osteoblasts
P
(Purkinje)
HV
Purkinje cells
N
(Neural)
HV
Brain and PNS,
(presynaptic terminal )
R
(Residual)
Intermediate
Voltage
Cerebellar granule
cells
T
(Transient)
Low Voltage
Pacemaker activity,
osteocytes
Presynaptic terminal
Ligand gated Ion channel in
Postsynaptic terminal

Cation channel ( Na+ or K+)
-
Lined with neg. charge, entrance becomes a bit larger
-
lets e.g. hydrated Na+ ions inside
- -> excitatory

-
Anion channel (Cl-)
Pos charged, opens , influx of Cl-
- ->Inhibitory
Ligand gated
2+
Ca
Channels

Examples:

cAMP ( of myocard cells)

IP3 (Inositol Triphosphat)  for IC Ca2+ depots

Ion channels in Sperms ( Cation)
-> functionally necessary for fertility and also fertilization
 Ca2+ can function itself as an intracellulary transmitter which
opens K+ channels or „fast“ Na+ channels (Silbernagl)
Division of Endocrinology, Central Drug Research Institute,
Lucknow, UP, India.
Cardiac muscle
Skeletal muscle
Already if Ca2+ drops 50% -> muscle tetany (lethal if respiratory)
Chloride channels
Cl
channels

Approximately 13 types

Neurones e.g. GABA ligand gated

Skeletal, cardiac and smooth muscle,

Cell volume regulation

E.g. CLC type (10-12 transmembrane helices)

-> CLC1 involved in reestablising resting membrane potential in
skeletal muscle cells

Also -> solute concentration mechanism in the kidneys
(abnormal function in thick ascending loop of Henle, associated
with Bartter´s syndrom renal salt wasting )
Cl
channels
- transepithelial salt transport,

Or cystic fibrosis transmembrane conductance
regulator (CFTR) gene

 cystic fibrosis

Genetic disorder

Gland secretions are abnormally thick

Chloride Ion Channels may be targeted as a
treatment for some Respiratory Diseases by
regulating abnormal mucus production.
Thank you for your attention !
Ion channel openers / closers
OPENERS

Diazoxide
-vasodilator used for
hypertension, smooth muscle
relaxing activity
CLOSERS

Amiodarone
- Used to treat cardiac
arrhythmias , prolonging the
repolarization
Yellow – in
Grey - out
Sources
http://www.creative-biogene.com/images/Ion-Channel.jpg
http://en.wikipedia.org/wiki/Membrane_potential#mediaviewer/File:Basis_of_Membrane_Potential2.png
http://www.nature.com/scitable/content/ne0000/ne0000/ne0000/ne0000/14615258/f1_marban_415213a-f1.2.jpg
http://www1.appstate.edu/~kms/classes/psy3203/Ear/hair_cell_tip.jpg
http://www.medbio.info/images/Time%203-4/wpeozyop.gif
http://upload.wikimedia.org/wikipedia/commons/thumb/e/e0/Synapse_Illustration2_tweaked.svg/2000px-Synapse_Illustration2_tweaked.svg.png
https://www3.nd.edu/~aseriann/nak.gif
http://www.uibk.ac.at/pharmazie/pharmakologie/images/cachannel.gif?m=e
http://www.neurology.org/content/68/3/233/F1.large.jpg
http://en.wikipedia.org/wiki/Sodium_channel#mediaviewer/File:Sodium_channel_phylogram.png = evolution of those channels
homepage: Alexander Chew:Florida State University;BSC5936;February 2005
http://upload.wikimedia.org/wikipedia/commons/4/45/GABAA-receptor-protein-example.png
http://cbsnews1.cbsistatic.com/hub/i/r/2010/09/22/86b3c5fb-a643-11e2-a3f0-029118418759/resize/620x465/9f5987c0e770cce5ce393581bd1aac6e/sperm_1.jpg
http://upload.wikimedia.org/wikipedia/commons/8/81/1ots_opm.png
Source: Mizutani S , "Milestones in the Evolution of the Study of Arrhythmias"
http://circep.ahajournals.org/content/2/2/185/F1.large.jpg
Literature:
(german book edition) Silbernagl; Taschenatlas Physiologie
guyton & Hall : textbook medical physiology
(german book edition) Golenhofen; Basislehrbuch physiologie (4th edition)