excitable membranes action potential & propagation Basic Neuroscience NBL 120 (2007)

ionic basis of APs action potentials: faithfully transmit information along the membrane (axon) of excitable cells allow rapid communication between distant parts of a neuron

action potentials the action potential is a regenerative electrochemical signal two distinct voltage-gated ion channels are responsible for action potential generation

the action potential 3 main stages: resting i.e. RMP depolarization reversal of membrane potential repolarization return of membranepotential to RMP

relationship between: membrane potential ion equilibrium potentials if the membrane becomes more permeable to one ion over other ions then the membrane potential will move towards the equilibrium potential for that ion (basis of AP). membrane potential (mV) EKEK E Na RMP E Cl general rule

depolarization rapid opening of Na-selective channels entry of Na “down” its electrochemical gradient 1. membrane more permeable to Na than K 2. membrane potential moves towards E na 3. because E Na is +ve the AP overshoots zero 4. At the peak of the AP Na is the primary ion determining the membrane potential

repolarization closure (inactivation) of Na-selective channels slower opening of K-selective channels 1. membrane more permeable to K than Na 2. membrane potential moves towards E K

the opening and closing of AP Na and K channels are controlled by changes in the membrane potential voltage-gated ion channels

properties (e.g. time course) of voltage- gated channels are more easily examined using the voltage-clamp holds or clamps the membrane constant movement of ions (current) through the channels is measured directly voltage-clamp

relationship between: membrane potential ion equilibrium potentials artificial manipulation of MP (voltage-clamp) - current will flow in the direction to move the MP towards the equilibrium potential of open ion channel membrane potential (mV) EKEK E Na RMP E Cl general rule

voltage-clamp used to rapidly change the membrane potential over the same range as occurs during the AP 2 current phases rapid / transient inward current slower outward steady current AP current time course

the inward phase carried by Na ions

selective agents block the 2 components 2 independent channels

all-or-none AP are not graded potentials threshold in order for an AP to occur the membrane must be depolarized beyond a threshold level inward Na overcomes resting outward K movement electrical stimulation synaptic activation what triggers an AP?

APs are regenerative activation of Na channels is cyclical initial depolarization opening of Na channels Na entry etc..

accomodation side-effects of inactivation disease (e.g. paramyotonia congenita)

action potential review Press button

membrane capacitance properties “bulk” solutions in and out are neutral the transmembrane potential difference exists within a narrow band just across the membrane capacitor: separates / stores charge

time constant changing the membrane voltage takes time charging a capacitor is not instantaneous inject current record voltage axon I V  m = r m c m

how can AP rise so fast?  m  r m c m

how electrical signals propagate passive decay length constant

length constant (passive process) axon / dendrite membrane resistance (r m ) axial, or internal, resistance (r i ) diameter (d) r m r i (+ r e ) =

AP propagation APs are conducted along excitable cell membranes away from their point of origin e.g. down the axon from cell soma to terminal

depolarization of the membrane during the AP is not restricted to a single spot the inward current carried by Na ions during the AP depolarizes adjacent portions of the membrane beyond threshold and the regenerative AP travels (in both directions) along the membrane local circuits

following a single AP a second AP cannot be generated at the same site for some time (absolute versus relative) Na channels need to recover from inactivation open K channels oppose inward Na movement refractory period

local circuit propagation is slow (< 2 m/s) In motorneurons propagation is fast 100 m/s Schwann cell envelop axons / layer of insulation increase resistance (Rm) (increase length constant) eliminate capacitance (time constant > 0) Nodes of Ranvier discontinuity in myelin sheath (every few 200+  m) myelination

saltatory conduction APs are only generated at Nodes of Ranvier high density of Na / K channels current flows rapidly between nodes little current leakage between nodes AP “jumps” down fiber as successive nodal membrane capacitances are discharged

propagation review Press button

myelination disease Charcot-Marie tooth disease progressive loss of PNS axons - weakness, atrophy Node of Ranvier Schwann cell

summary RMP electrochemical gradients Nernst equation AP initiation role of voltage-sensitive Na and K channels regenerative depolarization threshold and accommodation passive properties time and length constants capacitance AP propagation local circuits saltatory conduction