key review points:
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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 - PowerPoint PPT PresentationTRANSCRIPT
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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
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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
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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!
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Early sodium current during the action potential is due to the aggregate action of many individual sodium channels
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Later potassium current during the action potential is due to the aggregate action of many individual potassium channels
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Voltage dependence of open Na+ and K+ channel open probabilities mirrors the voltage dependence of Na+ and K+ conductances
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Voltage-dependent Na+ and K+ channelsGeneral concept
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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
General questions about ion channels
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Need to express ion channels in cells, in isolation from other channels:The Xenopus oocyte electrophysiology technique
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Types of ion channels
Further diversity gained through alternative splicing, editing, phosphorylation, mixing and matching of different subunit types
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Functional diversity Example: K+ channels
Nearly 100 known
Examples of functional variations:
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Molecular architecture of ion channels
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X-ray crystallography reveals mechanisms of ion permeation, selectivityKCsA bacterial ion channel
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Geometry of negative charges, pore size, and ion hydration work together to provide K+ selectivity, excluding Na+
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Mechanism of voltage sensitivity
TM4 contains charged residues; these move in the membrane when membrane potential changes
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Human neurological diseases are caused by ion channel mutations
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Kinetic properties of ion channels are finely-tuned, alteration of them causes disease
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Ion transporters:
Proteins that actively transport ions across membranes to establish concentration gradients
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Na+ efflux from the squid giant axon:
Sensitive to removal of extracellular K+
Sensitive to block of intracellular ATP generation
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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
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Transporter structures
Na+/K+ ATPase, deduced by mutagenesis
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The Ca++ pump: a more structure-based view