Potentials, Excitation and conduction · A, Typical smooth muscle action potential (spike...
Transcript of Potentials, Excitation and conduction · A, Typical smooth muscle action potential (spike...
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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