Electrical and concentration gradient driving forces for Sodium and Potassium How does the membrane potential change if 1) permeability to sodium increases 2) Permeability to potassium increases Why is resting membrane potential closer to E K than E Na ? What would happen to membrane potential if suddenly P Na became very great? Size and Direction of Arrows show driving forces! The G-H-K Equation! S 8

The Goldman Hodgkin Katz Equation If you know the concentrations of ALL permeable ions and their relative permeabilities, you can calculate the membrane potential using the GHK Equation. S 9

Na+ K+ ATPase maintains the concentration gradients across cell membranes Animation of the Pump What would happen to membane potentials and concentrations of Na+ and K+ if cells didn’t have this pump? S 11

Animations of the Origin of Resting Membrane Potential Animation of Resting Membrane Potential (single ion) YouTube animation of Na-K-ATPase, Sodium Co-transporter, and K Leak channels Origin of Resting Membrane Potential and intracellular recording S 12

Which ion moving in which direction (into or out of cell) is responsible for depolarization and overshoot? Which ion moving in which direction (into or out of cell) is responsible for repolarization and hyperpolarization? Can the membrane potential go more negative than -90 mV? Increase PK+ Increase PNa+ S 14 Increase PK+ How do ions get across the membrane? Ion channels!

Leak Channels Gated Channels ….. Ligand-gated ….. Mechanically-gated ….. Voltage-gated Interneurons & Motoneurons Sensory neuron Types and locations of Ion Channels Intracellular Recording Electrode or Stimulating Electrode S 3 w/ LGCs and MGCs w/ VGCs w/ LGCs

How is the intensity of a stimulus encoded by action potential if all action potentials have the same size (amplitude)? What happens when the membrane is depolarized by more than about 15 mV? Action potentials are all or nothing. Analogy of shutter release pressure on a camera, either trips shutter or not. S 4 Expanded on next slide

S 5 Relevance of the GHK equation Changes in membrane permeability produce changes in membrane potential via the opening and closing of ion channels!

To reset from inactivated state to closed state, membrane must repolarize. Compare and contrast voltage- gated Na and K channels based on time to open and duration of open time. Open at -55 mV Membrane must repolarize to “reset” Na+ Channels to be capable of opening again. S 6

Voltage-gated Na+ channel scienceblogs.com/.../upload/2006/03/channel.jpg Tetrodotoxin from ovary of Puffer fish, used in Japanese sushi (fugu) S 7

What types of ion-channels are labeled in this neuron in red? S 8 TTX with red fluorescent marker

Relative permeabilities Duration of AP Refractory periods absolute RP relative RP Properties of V-gated Na+ and K+ channels account for the shape of the action potential and the refractory periods. Why does the peak of the action potential not reach E Na ? Rising Phase Falling Phase S 9

S 10

Natural ways to Initate an Action Potential Graded depolarization in cell body reach threshold at axon hillock Graded depolarization in in receptive membranes of sensory neurons reach threshold for AP at trigger zone. i.e. nociceptors and stretch receptors. Unstable membrane potential cycles: pacemaker potentials in pacemaker cells of heart, smooth muscles of gut, and medullary neurons for respiratory rhythm. S 11

Who Cares? Novacaine, lydocaine, xylocaine, All block voltage-gated Na+ channels Prevent action potentials, so stimulus does not result in an action potential in sensory neurons which would convey that information to the brain where person would be conscious of the stimulus! S 12

Axon Hillock Axon Questions About Action Potential Conduction: How does an action potential move along the axon? Why doesn’t the amplitude get smaller with distance? Why is the conduction of an action potential unidirectional? What is the absolute refractory period and what is going on with voltage gated sodium channels that accounts for the absolute refractory period? What is the relative refractory period and what is going on with voltage gated sodium channels that accounts for the relative refractory period? S 13

In unmyelinated axons, action potential must be generated at each point along the membrane, a relatively slow process that involves influx of Na+ which sets up positive feedback cycle. In myelinated axons, action potential must be generated only at the nodes of Ranvier, which allows AP to be conducted much faster and with fewer ions moving, and thus less energetically expensive. S 14

Axon Hillock of interneuron or efferent neuron Axon The Questions: How does an action potential move along the axon? Why doesn’t the amplitude get smaller with distance? Why is the conduction of an action potential unidirectional? S 1 Trigger Zone of Sensory Neuron

Figure 6.23 AP CV (up to 100 m/s) Location of channels Energy Requirements Axon diameter Clustering of V-gated channels at Nodes of Ranvier Reminder: influx of Na+ is very quickly followed by efflux of K+ (not shown above) Saltatory Conduction S 3 What’s at the end of an axon?