Membrane and Action Potentials in Neurophysiology by University of Glasgow

Membrane and Action Potentials

·Dr Peter Moult .Peter.Moult@glasgow.ac.uk .341 Sir James BlackUniversity ofGlasgow MA VỊ HITẠI VỊŤA

Resting Membrane Potential

. A neuron at rest has a voltage across its membrane called a resting membrane potential

• This potential is determined by the concentration gradients of ions across the membrane and by the permeability of that membrane to each type of ion

. In a resting neuron there are concentration gradients across the membrane for Na+ and K+. Ions move down their gradients via channels, leading to separation of charge which establishes t resting potential.

Key Point

• The membrane is much more permeable to K+ than to Na+, so the resting potential is close to the equilibrium potential of K+ (the potential generated if the only ion in the system were K+)University ofGlasgow MA VỊ HITẠI VỊŤA

Potential Difference

Tricky but can be done in the lab. 10 12 14 16 Neuron 8 18 VOLTS Potential difference is the difference in potential between two points (e.g. either side of a membrane). i.e. the potential charge transfer if the impermeable membrane was removed.University ofGlasgow

Potential Difference Measurement

Filled micropipette Bath electrode Cell Bath Measurable by placing an electrode inside the cell and measuring vs bath electrode, outside the cell. Potential always quoted as inside vs outside.University ofGlasgow MA VỊ HITẠI VỊŤA

Membrane Potential (Difference)

Neuron -70 mV Resting potential (Exact value varies slightly between neuron types.)University ofGlasgow MA VỊ HITẠI VỊŤA

Concentration and Permeability of Ions

Outside Active Transport Na+ Na" Na+ Na+ (145 mM) K+ (5 mM) C1- (110 mM) Ca2+(2.5-5 mM) A" (25 mM) lon Extracellular Concentration* Intracellular Concentration* Relative Permeability Inside Na+ (5-15 mM) K+ (140 mM) C1° (4 mM) Ca2+(0.1 µM) Na+ 150 15 1 K+ 5 150 25-30 A" (147 mM) c1" Passive Redistribution K+ A" Na+ c1"University ofGlasgow MA VỊ HITẠI VỊŤA

Ion Channels and Movement

Why are ions where they are?

lon channels Permit / prevent ion movement across membrane · Selective for particular ions . Membrane-spanning protein complex · lon channels can be gated (open/close) · Various triggers activate (see later).University of Glasgow

Membrane Potential Change

How does the membrane potential change?

lon flow + I Opposite charges attract + Closed + Open (activated)University ofGlasgow LA VENTAI VỊTA + + + + + + + + + + Concentration (ionic) gradients also cause ions to flow + + + + + + + + + +University ofGlasgow

Ion Gradients in a Resting Neuron

Moderate [K+] K+ [K+] gradient + + + Low [K+] + + + + Na+ + + + + Low [Na+] Na+ + + + + High [Na+] + + + Neuron at rest + I.University ofGlasgow LA VENTAI VỊTA

Electrochemical Gradient

Equilibrium + + K+ + + + + Concentration gradient lonic gradient Chemical gradient + + Electrical gradient K+ Negative field pulls against exiting K+ + Electrochemical gradientUniversity ofGlasgow MA VỊ HITẠI VỊŤA

Equilibrium Potential

· K+ acting alone would establish an equilibrium potential of -90 mV. · Na+ acting alone would establish an equilibrium potential of +60 mV. · Resting membrane is 25 to 30 times more permeable to K+ than to Na+. · So resting membrane potential is closer to K+'s equilibrium potential.University ofGlasgow MA VỊ HITẠI VỊŤA

Ion Leakage and Na+/K+ Pump

· Na+ gradually leaks in - Makes interior slightly less negative - Reduces electrical gradient - K+ tends to leave cell (less negativity to pull back) · Solution: Na+/K+ pump - Membrane spanning protein complex - Requires energy (ATP) - (Actually even more important when nerve impulses are being generated - dealt with later in lecture series) - Pumps 3 Na+ out and 2 K+ in per cycle.University ofGlasgow MA VỊ HITẠI VỊŤA

Na+/K+- ATPase

Extracellular space Na+ + - Sodium Na+ Potassium K+ Plasma membrane Concentration Phosphate ATP ADP I + Cytoplasm K+University ofGlasgow MA VỊ HITẠI VỊŤA

Significance of Membrane Potential

So what?

Changes in membrane potential fundamentally underlie the entire operation of the nervous system both physiologically & pathophysiologically;

• Synaptic transmission
• Network communication
• All the sensory systems
• much much more ??? These processes could not occur without the establishment of an initial resting membrane potential.University ofGlasgow LA VENTAI VỊTA

Summary and Key Concepts

Summary & "What do I need know?"

• Understand the individual components required to establish a potential difference across a cell membrane
• Be able to explain the roles of different ion channels and pumps in establishing membrane potentials with reference to charged ions.
• Appreciate the importance of a potential difference for neuronal and nervous system function.
• Appreciate ion flow as a passive process driven by electrochemic; gradients, but also recognise the role of energy driven pumps. Main step up from Level 2
• Conceptualise the effect of altering ion concentrations either side of the membrane or selectively altering permeability and be able to relate this to certain pathophysiological states.University ofGlasgow MA VỊ HITẠI VỊŤA

Neuron Stimulation

What happens when a neuron is stimulated?

• By a neurotransmitter released by an adjacent neuron
• By an external chemical (olfaction & taste)
• By physical pressure (touch)
• etc ?
• lon channels are triggered to open
• Most important: Na+ channels
• Opening of Na+ channels is the key initial event in generating a nerve impulse.University ofGlasgow MA VỊ HITẠI VỊŤA

Potential Changes in Nervous System

Potential changes

Changes in membrane potential fundamentally underlie the entire operation of the nervous system;

• Synaptic transmission
• Network communication
• All the sensory systems
• much much more ???
• Broadly speaking, the two kinds of potential change are:
• graded potentials, act as short-distance signals
• action potentials, act as long-distance signalsUniversity ofGlasgow MA VỊ HITẠI VỊŤA

EPSPs & IPSPs

A postsynaptic potential (PSP) is the graded potential in the dendrites of a neuron that is receiving synapses from other cells. Postsynaptic potentials can be depolarizing or hyperpolarizing. Depolarization in a postsynaptic potential is called an excitatory postsynaptic potential (EPSP) because it causes the membrane potential to move toward threshold. Hyperpolarization in a postsynaptic potential is an inhibitory postsynaptic potential (IPSP) because it causes the membrane potential to move away from threshold.University ofGlasgow MA VỊ HITẠI VỊŤA

Graded Potentials Characteristics

· Occurs in active area of the membrane. · The magnitude of a graded potential varies directly with the magnitude of the stimulus. · Graded potentials spread decrementally by local current flow. · Flow is between the active area and adjacent inactive areas. · Graded potentials die out over a short distance.University ofGlasgow LA VỊHITAI VỊTA

Graded Potentials and Summation

Graded potentials

· Magnitude depends on the extent of stimulation . i.e. depends on quantity of ligand reaching neuron · Example 1: - One synapse with neuron (acting briefly): small depolarisation - More synapses (firing simultaneously): large depolarisation · Example 2: - One synapse repeatedly firing: large depolarisation · Adding together of stimuli = summation · 2 types of summation: - Spatial (as in Example 1) - Temporal (as in Example 2) · An individual graded potential from a synapse: Excitatory Post-Synaptic Potential (EPSP).University ofGlasgow MA VỊ HITẠI VỊŤA

Action Potential Graph

Action potential +70 +50 +30 +10 -10 -30 -50 Threshold potential -70 Resting potential After hyperpolarization -90 1 1 K > Time (msec) 1 msec Membrane potential (mV)University ofGlasgow MA VỊ HITẠI VỊŤA

Action Potentials Generation

Action potentials

· APs travel along axons · APs = nerve impulses · How are APs generated? · Why does breach of threshold potential cause runaway effect? · How and why do APs travel?University ofGlasgow

Voltage-Gated Ion Channels at Rest

At rest - Voltage-gated ion channels Voltage Sensing Domain V.S.D. Na+ postsynaptic neuron (soma or dendrite)University ofGlasgow LA VENTAI VỊTA

Supra-Threshold Potential

Supra-threshold + + Na+ from supra- threshold potential Voltage-gated ion channels + -55 mV + V.S.D. Na+ VSD = voltage sensing domainUniversity ofGlasgow MA VIHTAI VỊTA

Super-Threshold Ion Movement

Super-threshold ... + + + + V.S.D. + + Na+ + + Following electrochemical gradient. Voltage-gated ion channels + + + +University ofGlasgow

Runaway Effect of Voltage-Gated Channels

Super-threshold + + + + V.S.D. + + Na+ + V.S.D. + + +35 mV + Na+ + + I V.S.D. + + + Many voltage- gated channels in membrane Runaway effect. + + + + + + + + + + + + +University ofGlasgow MA VIHTAI VỊTA

Action Potential Ion Dynamics

Action potential + + + Na+ + + V.S.D. + + K+ + + V.S.D. + + Na+ + + +35 mV + + K+ V.S.D. + + Typical section of membrane V.S.D. V.S.D.University ofGlasgow LA VENTAI VỊTA

Action Potential Repolarisation

Action potential + V.S.D. Typical section of membrane + + Na+ + V.S.D. + + K+ + V.S.D. + + Na+ + + + K+ + V.S.D. + + Repolarisation Temporary hyperpolarisation (ca -90 mV) = 'undershoot' + + Movement of ions from slightly further away quickly corrects (-70 mV) K+ channels inactivated. K+ channel operation is delayed cf. Na+ channels + + Flows down electrochemical gradient + + V.S.D.4 Na K+ K+ channel opens (activation gate opens) ENa+ +60 +50 +40 +30 - +20 +10 - 0 Na+ channel opens and is activated (activation gate opens; inactivation gate already open) + PNa+, tPK+ > Na+ in > rising phase Na+ Na+ -10 - -20 -30 -40 -50 -60 -70 ECF Na I Threshold potential 6 1 8 Resting potential -80 EK+ -90 ICF Depolarizing triggering event Na+ channel reset to closed but capable of opening (activation gate closes; inactivation gate opens) K+ channel closes (activation gate closes) 3 + P Na+ K+ voltage-gated channel closed (activation gate closed) 5 K+ + PK+ 2 7 K+ Na+ voltage-gated channel closed (activation gate closed; inactivation gate open) Time (msec) Membrane potential (mV) University Na+ channel closes and is inactivated of Glasgow gate still open; inactivation gate closes)E Na+ channel closes and is inactivated (activation gate still open; inactivation gate closes) K+ channel opens (activation gate opens) Na+ channel opens and is activated (activation gate opens; inactivation gate already open) +PNa+, tPK+ Na+ channel reset to closed but capable of opening (activation gate closes; inactivation gate opens) K+ channel closes (activation gate closes) Na+ 3 +P Na+ K+ voltage-gated channel closed (activation gate closed) 2 ECF Na Threshold potential 6 8 Resting potential -80 EK+-90 ICF Depolarizing triggering event ENa+ +60 +50 - +40 +30 - +20 - +10- 0 - -10- -20- -30 -40 -50 -60 -70 Membrane potential (mV) 4 Na+ K+ Na+ in -> rising phase 5 K+ out -> falling phase Na+ K+ + P K + 1 7 K+ Na+ voltage-gated channel closed (activation gate closed; inactivation gate open) Time (msec)