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Sensory receptorsAction potential

12.11.2014.

� Sensory receptors

� Phases of the action potential

� Changes of ion fluxes corresponding to the different phases

Sensory receptors

Special type of cells which can collect and transfer different informations from the

environment.

Function: „translation”, signal processing.

Nerve fibreReceptors Central nervous system

stimulus: (physico-chemical) effect from the environment

→ metabolic changes inside the cells induced by a stimulus.

sensation: will involve the work of the CNS.

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Classification of sensory receptors

� Type of stimulus

• light-photoreceptors

• temperature-thermoreceptors

• pressure-mechanoreceptors…

� Localisation of the receptors

• head, ear…

� The origin of the information

• Exteroceptor (informations form the environment)

• Interoceptor (informations from the body)

• Proprioceptor (position of the different parts of the body)

Work of the receptors I.

� !

Local change in the receptor-potential

thresholdpotential Action-potential

frequency ~ strength of the stimulus

stimulus

„ALL OR NOTHING”

Nerve fibreReceptors Central nervous system

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Work of the receptors II.

t

Φ

Φthreshold

t

Urec

Uthreshold

t

Uaction

(Strength of the) stimulus

receptor

Nerve fibre-70 mV

0 mV

Action-potential

Below thethresholdlevel there isno sensation(no actionpotential).

The origin of the resting membrane potential

�Bernstein potassium hypothesis

�Nernst-equlibrium potential (electro-chemical potential)

�Donnan equlibrium: the membrane is impermeable for some components (e.g. intracellular proteins).

�Goldman equation: The membrane potential is the result of a „compromise” between the various equlibrium potentials, each weighted by the membrane permeabilityand absolute concentration of the ions.

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Equlibrium potential

Nernst equation: What membrane potential (E) can compensate (balance) the

concentration gradient (X1/X2).

2

1lnX

X

zF

RTE =

The inward and outward flows of the ions are balanced(net current = zero → equilibrium = stable, balanced, or unchangingsystem).

Ionic concentrations inside and outside of a muscle cell

[K+] ⇒ EmV = -58/1 log (139/2.5) = - 101.2 mV

[Na+] ⇒ EmV = -58/1 log (20/120) = + 45.1 mV

[Cl-] ⇒ EmV = -58/1 log (3.8/120) = + 86.9 mV

Na+ : 120 mM

K+ : 2.5 mM

Cl- : 120 mM

Na+ : 20 mM

K+ : 139 mM

Cl- : 3.8 mM

EmV=-92mV= 30.8 mV

Adjustablepower source

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→ a membrane-potential is not equal with

any of the equlibrium potentials for thedifferent ions� EmV_K+ = -101.2 mV

� EmV_Na+ = +45.1 mV

� EmV_Cl- = +86.9 mV

→ the ions are trying to move through the

membrane ⇒ „leakage”

Passive or leakage channels

EmV= - 92mV

„LEAKAGE CHANNELS”

K+

Na+Na+

K+

• Slow movement of the ions.

• Has to be compensated somehow.

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� The passive flux of Na+ and K+ (leakage) is balanced by theactive work of Na-K pump → contribution to the membranepotential.

� 3 Na+ move out vs. 2 K+ move in (exchanger)

� ATP (energy source) is needed

Na-K ATPase

● Ca2+ sensitive potassium channels (KCa)

● Inwardly rectifying potassium channels (KIR)

● “Tandem pore domain potassium channel” – “leak channel” (K2p)

● Voltage-gated potassium channels (KV)

� Sensitive (dependent) to voltage

changes in the membrane potential

Potassium channels

Islas LD, Sigworth FJ. Voltage sensitivity and gating charge in Shaker and Shab family potassium channels. J Gen Physiol. 1999 Nov;114(5):723-42.

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K+ channel (PDB: 1K4C)

membrane

Filter region

Gate

Interior of cell

K+ channel (PDB: 1K4C)

O2 K+

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Sodium channels

Bernstein,J.(1902).Untersuchungen zur Thermodynamik der bioelektrischen Strome. Pflugers Arch.ges. Physiol. 92, 521–562.

● Ligand gated sodium channels

● Voltage gated (sensitive, dependent) sodium channels

� contains a voltage sensor

� Sensitive (dependent) to voltage

changes in the membrane potential

Planells-Cases R, Caprini M, Zhang J, Rockenstein EM, Rivera RR, Murre C, Masliah E, Montal M. Neuronal death and perinatal lethality in voltage-gated sodium channel alpha(II)-deficient mice. Biophys J. 2000 Jun;78(6):2878-91.

Bernstein,J.(1902).Untersuchungen zur Thermodynamik der bioelektrischen Strome. Pflugers Arch.ges. Physiol. 92, 521–562.

● Ligand gated sodium channels

● Voltage gated (sensitive, dependent) sodium channels

� contains a voltage sensor

� Sensitive (dependent) to voltage

changes in the membrane potential

� activation gate (extracellular side)

� inactivation gate (intracellular side)

Planells-Cases R, Caprini M, Zhang J, Rockenstein EM, Rivera RR, Murre C, Masliah E, Montal M. Neuronal death and perinatal lethality in voltage-gated sodium channel alpha(II)-deficient mice. Biophys J. 2000 Jun;78(6):2878-91.

Sodium channels

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� Action potential: a momentary reversal of membrane potential (- 65mV to +40 mV) that will be followed by the restoration of the original membranepotential after a certain time period (1-400ms).

� Action potentials happens in different phases (depolarisation andrepolarisation).

� Action potentials are triggered by the depolarization of the membrane if itcan reach a critical value (voltage threshold).

� Action potentials are all or none phenomena

� any stimulation above the voltage threshold results in the same actionpotential response.

� any stimulation below the voltage threshold will not result action potentialresponse.

Action potential

Resting potential

Action potential (nerve cell)

Mem

bran

e po

tent

ial (

mV

)

time (ms)

0 1 2 3 4

Stimulus

Voltage threshold

~-70

~-50

0

~+40overshoot

Rising phase Falling phase

undershoot

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Equlibrium state

NaV channels:

� activation gate closed

� inactivation gate openResting potential

Voltage threshold

time (ms)

0 1 2 3

StimulusMem

bra

ne

po

ten

tial

(mV

)

~-70

~-50

0

~+40overshoot

Rising phase Falling phase

undershoot

Resting phase

The voltage-gated sodium channels will open-up if the

voltage threshold reached by a stimulus

NaV channels:

� activation gate open

� inactivation gate open

→ Na+ will move into the cell

→ the inner surface of the cell

will be positively charged

Resting potential

Voltage threshold

time (ms)

0 1 2 3

StimulusMem

bra

ne

po

ten

tial

(mV

)

~-70

~-50

0

~+40overshoot

Rising phase Falling phase

undershoot

Rising phase (depolarization)

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� The movement of the Na+

will slow down

� EmV_Na+ = + 45.1 mV

(Nernst – equilibrium

potential)

� Na+ channels will start to

form an inactive conformation

� K+ channels are starting to

open-up

Resting potential

Voltage threshold

time (ms)

0 1 2 3

StimulusMem

bra

ne

po

ten

tial

(mV

)

~-70

~-50

0

~+40overshoot

Rising phase Falling phase

undershoot

Overshoot

� All the voltage gated K+

channels are open� K+ move out from the

cell� NaV channels:

� activation gate open

� inactivation gate

closed→ refractory period

Resting potential

Voltage threshold

time (ms)

0 1 2 3

StimulusMem

bra

ne

po

ten

tial

(mV

)

~-70

~-50

0

~+40overshoot

Rising phase Falling phase

undershoot

Falling phase (repolarization)

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� The movement of the K+

ions will slow down� EmV_K+ = -101.2 mV

(Nernst-equlibriumpotential)

� The K+ channels will getinto a closed conformation

� The numerous and slowlyinactivating K+ channels willcause somehyperpolarisation

Resting potential

Voltage threshold

time (ms)

0 1 2 3

StimulusMem

bra

ne

po

ten

tial

(mV

)

~-70

~-50

0

~+40overshoot

Rising phase Falling phase

undershoot

Undershoot (hyperpolarization)

Resting phase

Resting potential

Voltage threshold

time (ms)

0 1 2 3

StimulusMem

bra

ne

po

ten

tial

(mV

)

~-70

~-50

0

~+40overshoot

Rising phase Falling phase

undershoot

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Recovery after the AP

� Intracellular ion concentrations change only a small amountwith each AP (0.0001% - 1%).

� Na+/K+ ATPases will slowly restore the original ionconcentrations.

� If the Na/K ATPases of a squid giant axon is poisoned, itcan still generate 100,000 impulses while the internalsodium concentration is increased only by 10%.

Absolute refractory period: The formation of a new AP is totaly blocked

Relative refractory period: larger depolarisation is needed than the

threshold to initialize an AP

Resting potential

Refractory period

Mem

bran

e po

tent

ial (

mV

)

time (ms)

0 1 2 3 4Stimulus

Voltage threshold

~-70

~-50

0

~+40overshoot

Rising phase Falling phase

undershoot

The cell is resistant to a stimulus. It is hard to get a response (action potential).

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Action potential in the cardiac muscle cells

Resting membrane potential

depolarisation•Na+ moving into the cell

plateau phaseEqulibrium between the Ca2+ release and the outward movement of the K+ ions

K+ ion moving out from the cell

K+ and Cl- ion movement

time (ms)0 ms 350 ms

~-90mV

~+35mV

Membrane potential

Resting membrane potential

Plateau: can help to direct the flow of the APs.

The end!!!