Lecture 5: Membrane Transport and Electrical Properties

Ion concentrations inside and outside the cells are often different

The relative permeability of a synthetic lipid bilayer

Two main classes of membrane transport proteins

Both:SpecificityMulti-TM

Hydrophilicsolutes crossmembrane via hydrophilic proteinpathway

(aka carriers, permases, or transporters)

Conformationchange

AqueousPores (faster)

Passive transport, active transport, electrochemical gradient

Ionophores are tools to increase permeability of membranes to specfic ions

Made by microorganisms

Mobile ion carriersChannel formers

A23187

Reversible conformational change in a carrier protein

Like an enzyme reaction--it saturates

Three ways of driving active transport

Active transport can be driven by ion gradients

Primary active transport: ATP-drivenSecondary active transport: ion-driven

Na is the usual co-transported ion

Binding of Na and glucose is cooperative

Binding ofNa and glucoseis cooperative

In bacteria, yeast and membrane organells proton gradient is more predominant

Lactose permease

Transcellular transport

Asymmetric distribution ofcarrier proteins

Na-K pump

Both Na and K are transported to higher [ ]

P-type transport ATPases Reversible!

F-type ATPases=ATP synthases

Work in reverse of transport ATPases

Chapter 14

ABC transporters

ATP binding=dimerization

MDR

ABC transporters:

1. Amino acids, sugars, ion, polysaccharides,peptides, proteins, flipping of lipids

1. MDR gene: hydrophobic drugs, chemotherapy2. Malaria: chloroquine3. Yeast mating pheromone4. Peptides from degration into ER5. Cystic fibrosis:regulator of Cl- channel

We will not talk about gap junctions herePorins stay in outer membrane of bacteria, mitochondria andChloroplastsChannels in the plasma membrane are narrow and selective And can open and close--ion channels, only “downhill”

Channels form hydrophilic pores, selective

Channels are “gated”

“Phosphorylation”, “desensitized”, “inactived”

A typical vertebrate neuron

Voltage-gatedNa+ channels

Voltage-gatedK+ channels

The “ball-and-chain” model of voltage-gated K+ channel inactivation

20 aa

Driven by state of lowest energy

Axon myelination

Schwann cells

JustbeginningTo myelinateaxon

More mature

Patch-clamprecording ofcurrent flowthrough Individualchannels

All or nothing

Conductance

Duration

Rate

synapses

Neuromuscular junctionis one of the best studied synapse

Acetylcholine receptoris the first ion channelto be purified, cloned, Reconstituted, recorded single channel,3-D structure

Cations: Na+, K+, Ca2+

Schematic structure of AchR

Ligand-gated ion channels

Five sets of channels are involved in neuromuscular transmission

(from a nerve impulse to muscle contraction)

Summary

1. Ions and larger polar molecules cannot cross the lipid bilayer;

2. Two types of transport proteins: carriers and channels;3. Passive and active transport;4. Three types of active transport;5. Mechanisms of cotransport;6. Na-K pump and ABC transporters;7. Channels: voltage-gated and ligand gated;8. Selectivity of K channels;9. Action potential, voltage-gated Na channel, voltage-gated

K channel, myelination;10. Single-channel recording;11. Neuromuscular junction as an example of synapse,

functions of ion channels.