Intro to Neurobiology Membrane excitability The action potential

Intro to Neurobiology Outline Passive and active conduction in neurons Action potential phenomenology Participating currents Voltage clamp experiments Voltage dependence: activation and inactivation Qualitative mechanistic description of action potential phenomenology

Intro to Neurobiology Reminder: passive conduction

Intro to Neurobiology Propagation of action potentials Depends on passive membrane properties Conduction velocity increases with λ And decreases with τ

Intro to Neurobiology Improving conduction velocity Increased diameter (squid…) –Problem: limited space Myelin –Increases R m –Decreases C –Allows energetically efficient signaling

Intro to Neurobiology Myelin PNS-Schwann cells –1 per internode CNS- Oligodendrocytes –1 per several axonal processes membrane wraps –Cytoplasm is squeezed out

Intro to Neurobiology Saltatory conduction Passive conductance in internodes Active AP regeneration in nodes of Ranvier

Intro to Neurobiology Differential channel constitution

Intro to Neurobiology Demyelination Slowing of conduction Desynchronization of different fibers Conduction block –Complete –At high frequencies

Intro to Neurobiology Conduction velocity Mylinated: –Aα m/s –Aβ30-80m/s –aδ5-30m/s Unmylinated: –C<2m/s

Intro to Neurobiology Geometrical considerations Theoretically, myelin=0.7 total diameter –Experimentally, Theoretically, internodes should be 100*d –Experimentally they are. Problems may arise at –Sudden expansion of membranes –Branching –Unmyelinated regions Safety factor

Intro to Neurobiology The action potential- phenomenology Rapidly conducting Non-attenuated Fast electrical signal

Intro to Neurobiology Characterized by Voltage overshoot All or none Refractoriness Accommodation phenomena –Accommodation to depolarization –Accommodation to hyperpolarization

Intro to Neurobiology All-or-none Explosive depolarization upon threshold crossing

Intro to Neurobiology Refractoriness Refractory period –Absolute: No amount of current will produce a second action potential –Relative: Second action potential will be achieved with only with larger currents

Intro to Neurobiology Accommodation phenomena Accommodation I –After prolonged depolarization subsequent APs to are Less frequent Smaller Depolarization block –Prolonged hyperpolarization Lowers threshold of action potential Increases its amplitude Anodic break response

Intro to Neurobiology Role of Na + and K +

Intro to Neurobiology Early clues Total conductance is increased during action potential (Cole and Curtis, 1938) Voltage overshoot at the peak of the action potential (Hodgkin and Huxley, 1939) Rapid repolarization of the membrane

Intro to Neurobiology Early findings Action potential amplitude depends on extracellular Na + concentration (Hodgkin and Katz, 1949)

Intro to Neurobiology Participating currents Hodgkin Huxley experiments Captured voltage dependence and kinetics of the participating currents in the squid giant axon

Intro to Neurobiology Recall I ion =g ion (V m -E ion ) g ion =I ion V m -E ion But they are interdependent: g(V m )V m (g) I total =I C +I R

Intro to Neurobiology Voltage clamp setup V m is controlled Vm=Vc After 1 st step

Intro to Neurobiology Voltage clamp experiments I early =I total -I late substitute Na + out with cholineH +

Intro to Neurobiology Or use selective neurotoxins TTX - High affinity voltage dependent Na + channel blocker Saxitoxin -’’- Cocaine – Low affinity voltage dependent Na + channel blocker TEA - Low affinity voltage dependent K + channel blocker

Intro to Neurobiology Na+ and K+ currents Note: direction time course inactivation

Intro to Neurobiology Voltage dependence

Intro to Neurobiology IV curve

Intro to Neurobiology Single channel recordings

Intro to Neurobiology Activation Activation: Increased probablity of channel opening with depolarization Deactivation: decreased probability of channel opening with repolarization

Intro to Neurobiology Peak conductance (V m ) g ion =I ion V m -E ion

Intro to Neurobiology Peak conductance (t)