Potentials, Excitation and conduction · A, Typical smooth muscle action potential (spike potential) elicited by an external stimulus. B, (Repetitive spike potentials, elicited by

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Potentials,

Excitation and

conduction

Potentials,

Excitation and

conduction

Negative resting membrane

potential in all of the cells:

Min: -10mV

Max:-90 mV

Extracellular: Intracellular:• Na+: 140 mmol/l

• K+: 4 mmol/l

• Ca2+: 2.5 mmol/l

• Mg2+: 1 mmol/l

• Cl-:103 mmol/l

• HCO3-: 24 mmol/l

• Phosphates: 1 mmol/l

• Glucose: 3-6 mmol/l

• Urea: 2.5-6 mmol/l

• Plasma protein: 60-80 g/l

• Interstitial protein: 0-60 g/l (mean: 10 g/l)

• Na+: 10 mmol/l

• K+: 160 mmol/l

• Ca2+: 0.25 µmol/l

• Mg2+: 15 mmol/l

• Cl-: 5 mmol/l

• HCO3-: 5 mmol/l

• Phosphates+organic aniones: 135 mmol/l

• Protein : 200 g/l

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• When an ion on one side of a membrane can not diffuse

through the membrane, the distribution of other ions to

which the membrane is permeable is affected in a

predictable way.

Donnan Effect

X Y

• K+ 100 100

• Cl– 50 100

• Protein– 50

• Cl– diffuses from Y to X, and some K +

moves with Cl –. K+x>K+

y

•[K+x] + [Cl–

x] + [Prot–x] > [K+

y] + [Cl–y]

• [K+x] [Cl–

y]

•— — = — — —

• [K+y] [Cl–

x]

•Gibbs-DONNAN equation:

•[K+x] [Cl–

x] = [K+y] [Cl–

y]

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Significance

• 1. More osmotically active particles are

intracellularly (it will be restored by Na-K pump)

• 2. A potential difference exists across the membrane

(about – 10 mV).

• 3. Since there are more proteins in plasma than in

interstitial fluid, there is a Donnan effect on ion

movement across the capillary wall.

Equilibrium potentialThe membrane potential at which equilibrium exists between

concentration gradient and electrical gradient for one ion.

Nerst equation for positive ions:

Ei= -61x log CIC/CEC (mV)

Mammalian neuron

Ion IC

(mM)

EC (mM) Equilibrium potential

mV

Na+ 15 145 +61

K+ 150 4.0 -97

Cl- 10 110 -88

Ca2+ 10-4 1.25 +126

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Membrane potential:

Goldman-Hodgkin-Katz equation:

-58 log PK+[K+i]+PNa+ [Na+i]+PCl- [Cl-e]

PK+ [K+e]+PNa+[Na+e]+PCl-[Cl-i]

•Depends:

–Polarity of the electrical charge of each ion

–Permeability of the membrane to each ion

–Concentration of the respective ions on both sides

–Na+-K+- pump; Donnan effect

•Resting membrane potential: -10- -90 mV !

Membrane potential changes

•Electrotonic potential

•Action potential

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Electrotonic potential

Characterestics

• The amplitude depends on the intensity of stimulus

• Hyperpolarization or depolarization

• The potential changes decrease in space(decrementer spreading) =>Local potentialchanges

• No refracter period => summation (spatialand temporal)

• (Subthreshold stimulus)

•Amplitude

correlates with the

intensity of

stimulus

•Hyper- or

depolarization

•Decrementer

spreading

Summation

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Mechanisms

• Opening/closing of different ion channels

Types

– EPSP (e.g. glutamate)

– IPSP (e.g. GABA)

– Fast: effects of ionotropic receptors

– Slow: effects of metabotropic receptors

Significance

• In all cells => changes in cell functions

E.G.

• Sensory receptors (eye, ear, touch etc.)

– Stimuli: mechanical, chemical, electromagnetic, thermal

– Primary sensory receptors (muscle, tendon, skin-, mucosal-,

joint- receptors)

– Secondary sensory receptors (inner ear, taste)

– Tercier sensory receptors (eye)

– Generator potential: the threshold for action potential.

• EPSP, IPSP caused by neurotransmitters on the bodies and

dendrites of neurons.

• Releases of hormones, cytokines etc.

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Rapid changes in the membrane potential after threshold

(15 mV) or suprathreshold stimulus, that spread rapidly

and constantly along the cell membrane.

Stages•Resting stage (- 60 - 90 mV)

•Depolarization stage

– Initial depolarization (15 mV)

– Fast depolarization

– Overshoot (max: +30-+40 mV)

•Repolarization stage

– Fast repolarization

– After-depolarization

– After-hyperpolarization

Action Potential

Characteristics

• Evoked by depolarization

• Threshold/suprathreshold stimuli (15 mV)

• „All or None” law: The amplitude does not depend on the intensity of stimulus (constant).

• The potential changes do not decrease in space (non-decrementer spreading) =>Propagation of AP along the membrane (Non-local potential changes).

• Refracter periods (absolute, relative) => NO summation

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Permeability changes

(opening of voltage gated ion

channels)

Depolarization:

Opening of fast voltage-

gated (TTX-sensitive) Na+

channels => Peak depends

on EC. Na+ cc.;

Pozitive feed-back

Repolarization:

Inactivation of voltage

gated Na+ channels

Opening of voltage gated

K+ channels (TEA-sensitive)

Mechanism

Inhibitor:

Tetrodotoxin

Inhibitor: Tetraethyl

ammonium

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Calcium ion regulates the

opening of the voltage-gated

sodium channels.

Normal Ca-level: Threshold for

AP is 15 mV depolarization

High Ca-level: Threshold for

AP is higher than15 mV

depolarization

Low Ca-level: Threshold for

AP is lower than15 mV

depolarization => enhanced

excitability in neurons and

skeletal muscle => tetany

Role of calcium ion in the excitability

*total* Na+

* K +

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Special action potentialsHeart muscle cells

Voltage gated L-type Ca2+ channels

Special action potentials

• Heart pacemaker cells

Smooth muscle

Neurons

• Repetitive discharge

• Voltage gated T- és L-type

Ca2+ channels

More leaking (funny) Na+

channels

• There is no fast voltage gated

Na+ channels

•

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• Smooth muscle AP

• Voltage gated L-type Ca2+ channels

A, Typical smooth muscle action potential

(spike potential) elicited by an external

stimulus.

B, (Repetitive spike potentials, elicited by slow

rhythmical electrical waves that occur

spontaneously in the smooth muscle of the

intestinal wall.)

C, Action potential with a plateau, recorded

from a smooth muscle fiber of the uterus.

Special action potentials

Comparison of APs

Nerve Skeletal m. smooth m. heart m

resting pot (mV) *-80-90 *-80-90 *-40-60 *-80-90

duration of AP

(ms) *0.2-2 *1-5 20-300 300

latency (ms) *1-4 *50 0

duration of

contraction (ms) *10-100 *200-3000 300mechanism of

AP Na in Na in Ca in Na, Ca in

innervation somatic autonomic autonomicinhibitory

innerv. no may be may be

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Duration of action potentials

•Development of AP in neurons: Axon hillock

•Conduction of AP

–Non-myelinated nerves

–Myelinated nerves

• Saltatory conduction: node of Ranvier

•Distribution of ion channels

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Diameter (µm) Conduction velocity

(m/s)

Function

Aα 15 70-120 Proprioception, somatic motor

Aβ 10 30-70 mechanoreception, somatic motor

Aγ 5 15-30 Somatic motor

Aδ 3 13-30 Pain, temperature, mechanoreception

B 2 3-15 Preganglionic autonomic

C 1 0.5-2 Pain, temperature, mechanoreception,

postganglionic sympathetics

NerveNerve fiberfiber typestypes

((ErlangerErlanger//GasserGasser divisiondivision))

Number Origin Fiber-type

Ia Muscle spindle Aα

Ib Tendon organ Aα

II Muscle spindle, touch, pressure Aβ

III Pain, heat, touch Aδ

IV Pain, heat C

Lloyd/Lloyd/HunfHunf divisiondivision

Compound action potential

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•The role of action

potentials:

– Neurons: releases of

transmitters,

neuromodulators

– Muscle: contraction

• Coding of stimuli

intensity:

– Frequency

– Population

Comparison of electrotonic and action

potentials

Comparison of electrotonic and action

potentials

•Subthreshold

•Correlate with intensity

•Depol or hyperpol

•Passive conductance

•No refractory stage

•Spatial and temporal

•Amplitude/analog

•Decrementer

•Threshold, suprathreshold

•Independent from intensity

•Deloparization

•Voltage gated channels

•Refractory stages

•No

•Frequency/digital

•Non-decrementer

EPEP APAP•Stimulus

•Amplitude

•Direction

•Ion current

•Excitability

•Summation

•Code of

intensity

•Spreading

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• Local anesthetics

– bind to the opened fast voltage-gated Na+ channels,

then block them

• Veratridin

– maintains the opened state of the fast voltage–gated

Na+ channels

Susceptibility to Most Intermediate Least

Hypoxia B A C

Pressure A B C

Local anesthetics C B A

Veratrum