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Key Review Points: 1. Electrical signaling depends on the motion of ions across neuronal membranes 2. Na + , K + , Cl - and Ca ++ ions are distributed unequally across neuronal membranes 3. At rest, diffusion of these ions creates the membrane potential
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Key Review Points: 1. Electrical signaling depends on the motion of ions across neuronal membranes 2. Na+, K+, Cl- and Ca++ ions are distributed unequally across neuronal membranes 3. At rest, diffusion of these ions creates the membrane potential 4. Rapid changes in ionic permeability cause transient, self-regenerating changes in the membrane potential known as action potentials, which carry information
Today’s Lecture: Ion channels: proteins that form pores in the membrane to permit ions to cross Ion transporters: proteins that actively transport ions across membranes to establish concentration gradients
New technology: The patch clamp technique The voltage clamp technique shown before was adequate for large currents, but produced large ‘background noise’ ‘Patch clamp’ technique has superior signal-to-noise ratio, so very small currents can be measured, even down to the current passed through a single ion channel!
Early sodium current during the action potential is due to the aggregate action of many individual sodium channels
Later potassium current during the action potential is due to the aggregate action of many individual potassium channels
Voltage dependence of open Na+ and K+ channel open probabilities mirrors the voltage dependence of Na+ and K+ conductances
Voltage-dependent Na+ and K+ channels General concept
General questions about ion channels How can a protein sense voltage? How does it respond respond with the appropriate timing? How does it permit some ions to cross the membrane while excluding others? How does it inactivate? --> Functional studies of ion channel proteins
Need to express ion channels in cells, in isolation from other channels: The Xenopus oocyte electrophysiology technique
Types of ion channels Further diversity gained through alternative splicing, editing, phosphorylation, mixing and matching of different subunit types
Functional diversity Example: K+ channels Nearly 100 known Examples of functional variations:
X-ray crystallography reveals mechanisms of ion permeation, selectivity KCsA bacterial ion channel
Geometry of negative charges, pore size, and ion hydration work together to provide K+ selectivity, excluding Na+
Mechanism of voltage sensitivity TM4 contains charged residues; these move in the membrane when membrane potential changes
Human neurological diseases are caused by ion channel mutations
Kinetic properties of ion channels are finely-tuned, alteration of them causes disease
Ion transporters: Proteins that actively transport ions across membranes to establish concentration gradients
Na+ efflux from the squid giant axon: Sensitive to removal of extracellular K+ Sensitive to block of intracellular ATP generation
Usually, the Na+/K+ ATPase has only a small direct effect on membrane potential, (<1 mV) because it is very slow compared to ion flux through ion channels However, it can have a larger effect if in small-diameter axons, where the ratio of surface-area to cytoplasm volume is small and ion concentrations change appreciably
Transporter structures Na+/K+ ATPase, deduced by mutagenesis
