11 MZB I - Devuyst

• The boundary of cells is mostly constituted of a lipidic material
• Non-lipophilic substances (incl. water) must use specific pathways

Channel-like Integral Membrane Protein

-> Extremely abundant in RBCs (redbloodcells)

-> billions of water moleclues can cross the pore per second

Ligand gated
Phosphorylation-gated
Voltage-Gated
Stretch or pressure Gated

Voltage-gated Ion Channel

Na+ channels can exist in three distinct states: deactivated (closed), activated (open), or inactivated (closed).

When the membrane is at its normal resting potential, Na+ channels are in their deactivated state, blocked on the extracellular side by their activation gates. In response to an action potential, the activation gates open, allowing positivelycharged Na+ ions to flow into the cell (e.g. neuron), causing the voltage across the neuronal membrane to increase. Because the voltage across the membrane is initially negative, as its voltage increases to and past zero, it is said to depolarize. This increase in voltage constitutes the rising phase of an action potential.

At the peak of the action potential, when enough Na+ has entered the neuron and the membrane's potential has become high enough, the Na+ channels inactivate themselves by closing their inactivation gates. Closure of the inactivation gate causes Na+ flow through the channel to stop, which in turn causes the membrane potential to stop rising. With its inactivation gate closed, the channel is said to be inactivated. With the Na+ channel no longer contributing to the membrane potential, the potential decreases back to its resting potential as the neuron repolarizes and subsequently hyperpolarizes itself This
decrease in voltage constitutes the falling phase of the action potential.

When the membrane's voltage becomes low enough, the inactivation gate reopens and the activation gate closes in a process called deinactivation, or removal of inactivation. With the activation gate closed and the inactivation gate open, the Na+ channel is once again in its deactivated state, and is ready to participate in another action potential.

voltage-dependent potassium ion channel
-> "paddles" that open and close in response to positive and negative charges

- Post-synaptic membrane
- Ligand-gated channels (ion channel part of the receptor)
- Depolarization -> excitation

• Ionotropic and metabotropic receptors are both ligand-gated transmembrane proteins.
• Ionotropic receptors change shape when they are bound by a ligand. This change in shape creates a channel that allows ions to flow through.
• Metabotropic receptors do not have channels.
• Metabotropic receptors activate a G-protein that in turn activates a secondary messenger, that in turn will activate something else.
• Metabotropic receptor activation may or may not result in the opening of ion channels somewhere else on the membrane.

Single Channel Recording 

Facilitated Diffusion – Passive

Carriers are Saturable: Kinetics
-> Michaelis-Menton

Carriers can Transport One or Several Substrates

Uniporter

GLUT1 : Glucose Transporter der GLUT Familie
- Diffusion of D-Glucose in one in direction
  ->According to concentration gradient to concentration
• e.g. in red blood cells 

s.B.

Chloride-Bicarbonate Exchanger; involved in the elimintaion of CO2

Primary active transport: coupling
Direct coupling between energy and transport
(ATPase and ABC Transporter)

Secondary active transport:
Indirect coupling between energy and transport
(e.g. Na/Glucose Symporter)
-> Da Na+ in die Zelle gelangt, welches anshcliessend von der Na+/K+ Pumpe wieder aus der Zelle herausgepumpt werden muss -> sekundär

P-class Pumps

V-Class proton Pumps

F-Class Proton pumps

ABC superfamily

-> Diese ATPasen bauen einen Ionengradienten unter Hydrolyse von ATP auf.

Plasma membrane of plants, fungi, bacteria (H+ Pump)

Plasma membrane of higher eukaryotes (Na+/K+ Pump)

Apical lasma membrane of mammalian stomach (H+/K+ pump)

Plasma membrne of all eucaryotic cells (Ca2+ pump)

Sarcoplasmic reticulum membrane in muscle cells (cCa2+ pump)

Inside: Potassium

Outside: Sodium

p-class

Electrogenic Transport: 3 Na+ auswärts, 2 K+ einwärts
 -> delta: one positive charge auswärts
 -> Verbraucht ca. 25% des ATP (Mensch)

P-class

located on the plasma membrane and the ER
-> pumps Ca2+ out of the cytosol

s.B.

Diese ATPasen bauen einen Protonengradienten unter Hydrolyse von ATP auf. Sie sind nur in den Vesikeln der Endo- und Exozytose sowie inLysosomen, Endosomen und Golgi-Vesikeln der Eukaryoten und in den Vakuolen von Pflanzen und Hefepilzen zu finden. Sie steuern den pH-Wert in den Vesikeln.

s.B.

iese ATPasen nutzen einen Protonengradienten zur Synthese von ATP aus ADP. Sie werden daher als ATP-Synthasen bezeichnet und sind sowohl bei Eukaryoten in denChloroplasten und in den Mitochondrien als auch bei Prokaryoten zu finden

lysosomes: the place where Proteins are destroyed "garbage system of the cell"
-> lysosomes are acidic: pH<5

ABC-Transporter bilden eine große Familie von Membranproteinen, die als gemeinsames Strukturelement eine ATP-bindende Kassette (von englisch: ATP binding cassette, ABC) besitzen und spezifische Substrate aktiv über eine Zellmembran transportieren
-> Transporter for phospholipides, lipophilic substances

MDR1: Multidrug-Resistance Protein
Pumps toxic substances out of the cells –> resistance to chemotherapy

Example of ABC Transporter : CFTR (Cystic Fibrosis Transmembrane Conductance Regulator)

•Epithelial Cl- channel

-> Mutationen können zu zystischer fibrose führen

In secondary active transport, also known as coupled transport or co-transport, energy is used to transport molecules across a membrane; however, in contrast to primary active transport, there is no direct coupling of ATP; instead it relies upon theelectrochemical potential difference created by pumping ions in/out of the cell
-> cotransporter

- A cell without a rigid cell wall is unable to withstand hydrostatic pressure differences.
• In case of acute changes in extracellular osmolality, the cells respond with activation of various transport systems in order to adapt the cell volume. These reactions lead to Regulatory volume increase (RVI) or Regulatory volume decrease (RVD).
• During chronic changes in extracellular osmolality, the cells respond by changing the intracellular concentration of organic osmolytes (e.g. betaine, taurine).

285-290 mOsm/kg H2O

sodium is the most important kation

s.B.

Volume regulatory electrolyte gain and loss are mediated by rapid changes in membrane transport

- Advantages: allows cell to rapidly correct their volume by activating pre-existing transport pathways
- Disadvantages: disruption of intracellular ion concentrations and cytoplasmic ionic strength

s.B.

- Signals: mechanical stress; dilution and concentration of cytoplasmic constituents
- Signal transduction: kinases and phosphatases

a) b) Apical (luminal) membrane
c) Endo-pinocytosis apparatus
d) Basolateral membrane 
1: Transcellular pathway
2: Paracellular pathway

Tight Junctions (engl. für „dichte Verbindung“, lat. Zonula occludens, in deutscher Literatur auch „Schlussleiste“) sind schmale Bänder aus Membranproteinen, die Epithelzellen von Wirbeltieren vollständig umgürten und mit den Bändern der Nachbarzellen in enger Verbindung stehen

Must have low levels of intracellular Na+ to drive transepithelial transport

• Primary active transport
• Secondary active transport
• Facilitated diffusion