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: Specificity Multi-TM Hydrophilic solutes cross membrane via hydrophilic protein pathway (aka carriers, permases, or transporters) Conformation change Aqueous Pores (faster)

Passive transport, active transport, electrochemical gradient

Ionophores are tools to increase permeability of membranes to specfic ions Made by microorganisms Mobile ion carriers Channel 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-driven Secondary active transport: ion-driven Na is the usual co-transported ion

Binding of Na and glucose is cooperative Binding of Na and glucose is cooperative

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

Transcellular transport Asymmetric distribution of carrier 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, chemotherapy 2.Malaria: chloroquine 3.Yeast mating pheromone 4.Peptides from degration into ER 5.Cystic fibrosis:regulator of Cl- channel

We will not talk about gap junctions here Porins stay in outer membrane of bacteria, mitochondria and Chloroplasts Channels 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-gated Na+ channels Voltage-gated K+ channels

The “ball-and-chain” model of voltage-gated K+ channel inactivation 20 aa Driven by state of lowest energy

Axon myelination Schwann cells Just beginning To myelinate axon More mature

Patch-clamp recording of current flow through Individual channels All or nothing Conductance Duration Rate

synapses

Neuromuscular junction is one of the best studied synapse Acetylcholine receptor is the first ion channel to 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.