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

Yellow – in
Grey - out
 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
 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
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)
 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 High Skelettal muscle,

(Long-lasting) Voltage smooth muscle,
osteoblasts
P HV Purkinje cells
(Purkinje)

N HV Brain and PNS,

(Neural) (presynaptic terminal )

R Intermediate Cerebellar granule

(Residual) Voltage cells

T Low Voltage Pacemaker activity,

(Transient) 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 Ca 2+ 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 CLOSERS
 Diazoxide  Amiodarone
-vasodilator used for - Used to treat cardiac
hypertension, smooth muscle arrhythmias , prolonging the
relaxing activity repolarization
 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)