You are on page 1of 48

PHYSIOLOGY

IONIC EQUILIBRIUM PRINCIPLES


1. Membrane Potential (Em)
Electrical charge (voltaje) across
+
[ ]-High
[+ ]-Low the membrane
[+] LOW 2. Electrochemical gradiente
[+ ] LOW Combination of chemical
1 (concentration) and electrical
[] LOW
gradientes influencing the
- + diffusion of ions

[+ ]High
3. Equilibrium potential
Membrane potential that puts an
Em: -70mV ion in electrochemical equilibrium
No NET diffusion
[]-High [+]-High
EXAMPLE
PRINCIPLES Em=-70mV
Ek = -90mV
ECl= -80mV
4. Conductance (g)
Flow of ion across the cell ENa = 60mV
membrane. Relates to NET FORCE for K
permeability of the cell + = -70 (-90) = 20mV
membrane to an ion
NET FORCE for Cl
5. Driving Nforce (ET FORCE) = -70 ( -80) = 10mV
Resting membrane potential
minus equilibrium potential NET FORCE for Na
+ = -70 (+60) = 130mV
ION CHANNELS Classes of Ion channels
Ungated (leak)
Always open

NMDA Receptor
Voltage-gated
Ligand and Voltage- Open/Close
gated

Ligand-gated
(Receptor for ligand)
ION CHANNELS
1. Ungated channels
Always open that means high conductance for the ion
2. Voltage-gated
If the gated is close the conductance is LOW
If the gated is open the conductances is HIGH
3. Ligand-gated Conductance is related
If the ligand binds the channel it will open to permeability
4. Ligand/voltage-gated (NMDA)
If membrane potential is more negative than 70mV the Mg2+ Blocks the Channel
If the membrane potential is less negative than 70mV so the Mg2+ goes away
The channel will open is the ligand binds to the receptor
GLUTAMATE AND ASPARTATE (excitatory amino acids)
NMDA is involved in memory and pain
ION CHANNELS
Blockers of NMDA Inhibit pain
Phencyclidine (PCP)
Ketamine (dissociative anesthetic drug)

NERNST EQUATION
Calculates the equilibrium potential for each
ion
the equilibrium puts an ion in
electrochemical equilibrium.
EQUILIBRIUM POTENTAL
The oin ALWAYS diffuses in a direction that brings the Membrane potential
(Em) towards its equilibrium

The overall conductance of the ion would be ralaterd to the force and the
permeability (determined by ion channels state) of the membrane for the ion

The membrane potential (Em) moves toward to the equilibrium potential of


the most permeable ion

The number of oins that actually across the membrane is negligible. It wont
change concentration
Increased excitability

Membrane potential
Depolarization Moves toward ZERO
becomes less negative
Em

Membrane potential Moves further from


Hyperpolarization
becomes more negative ZERO

Decreased excitability
High[ + ] outside It's closer
[+ ]High + the membrane Depolarizes
to fighter
an action
potential
+ Stays in the cell or Increased
Less + goes out the acutely
Em: -70mV - + cell excitability

+
Decreased
concentration Pathology
gradient

Em less negative
Em move toward Hyperkalemia +
ZERO

Depolarizes the
membrane Arrhythmias
+ + Hyperpolarizes

[+ ]High - +
Loose
Em would be excitability
Em: -70mV more negative
(-95mV)
Its more
negative Em
+ moves
outside of the
membrane
Pathology

Hyperpolarizes
the membrane Hypokalemia +
Excitability Fatal arrytmias
Hypokalemia
Hyperpolorizes Increased K+ tend to move
concentration outside the cell
gradient membrane
K+ Acutely
Hyperkalemia excitability
Depolarizes
Decreased
That makes K+
concentration
stay in the cel
gradient
Outside High It has very low

[ ] conductance

(104 mmHg)
[ ] Low - + Changes in extracellualar
concentration have minimal
impact on resting
membrane potencia
Concentration
Em: -70mV gradient moves
inside in the cell Conductance

Hyperpolarizes
Low concentration Em move toward -76
of [ ] inside the
cell
Em move to
equilibrium

Electrical gradiente
is to move outside
the cell because is a moves inside
negative charge
Outside High It has very low
+ [+ ] conductance
(140 mmHg)

[+] Low - + Very low resting


conductance
Changes in extracellualar
concentration have minimal
impact on resting membrane
Theres
more Na
+ Doesn't potencia ousite the
Low concentration
easily cross inside the cell membrane
Em: -70mV
Concentration
gradient is to go in
Its a positive
+ ~ +70mV charge and
Em is
Electrical gradiente is negative so
to in Na moves in

If +
Conductances
Em move to Na moves in
equilibrium because Em
Em will will do to
be less Equilibrium of
Na +70mV
It will depolarizes negative
the membrane If +
Conductances
EXAMPLE
Em=-70mV Ek = -90mV Cl conductance
ECl= -80mV ENa = 60mV The ion would move into the cell
Em will move toward ECl
[+ ]-High
K+ conductance
[]-High
The ion would move out of the cell
Because + is a positive charge and the
membrane potential would move toward
[+] LOW 90mV
[+ ] LOW
- + To make it more negative the K has to go
[] LOW
out of the cell
[+ ]-Low
+
[ ]High + has a higher concentration inside the
cell membrane
Em: -70mV
[+]-High
High [ + ] intracellular
High [+ ] extracellular
ATP is needed to move the ions in and out
+ + is pumping 3+ in and
2 + out
The cell membrane is not 100% impermeable to
+ + .
+ leaking in and + leaking out, thats why
the + + put them back where
they belong.
At rest, inward and outward ion leakage is
balanced by the pump, producing a steady-state
3+ out; 2+ in makes inside more
negative so the pump is Pharmacology
electrogenic
This movement of ions through
Drugs the blocks the
the PUMP cause water to leave pump
the cell
Thats why the +
Digoxin
+ pump is important Digitalis
to regulate cell volumen
Action potential is a rapid depolarization followed by a
repolarization

Function
Nerves: Conduction if neuranal signal
Nerve to nerve
Nerve to tissue
Muscle: initiates contraction
The resting membrane The actions potential
Nerves: 70mV Repolarization
Depolarization
Muscle: - 90mV
Cardiac muscle: -90mV
In muscle cell theres is more
+ conductances at rest
It means grater +
conductances
In nerves the + conductances
is lower than muscle
The Fast + channel is
involved in depolarizaion
+
FAST CHANNELS Decreased
conductance
Close state of +
Low conductance
for + High conductance
for+ because the
The kinetics of the + channel gated is open
makes them very fast
Resting Open by
Despolarization
Open (Activated) Inactivated by
Positive membrabe potential
Inactivated Resting by
Repolarization
It cant go from
Resting Em Open to Resting
Em = Negative

Depolarization
It will open fast Na
Repolarization channel
FAST SODIUM

Positive
membrane
CHANNELS

potential

Open
Inactivated
Activated
They Block the Fast + Channels
Tetrodotoxin (TTX)
Saxitoxin (STX)
BLOCKS FAST +
Cain Drugs
Channels
They block the production of
action potential
Ciguaton (CTX
Batrachotoxin (BTX)
BLOCKING THE
+ Channels stay in the
INACTIVATION
OPEN STATE a Little bit
longer
Extracellular Calcium BLOCK Decreased
the fast + Channels excitability

Hypocalcemia Calcium Decreased


BLOCKS the fast + Channels excitability

Hypercalcemia Calcium Its going to depolarizes the membrane more faster


OPENS the fast + Channels Increased excitability
IN THE FAST +
Initially excitability
CHANNELS Overtime excitability
Depolarizes
Hyperkalemia Concentration gradient
Because + stays in the cell Some fast + will open by
depolarization
Overtime they will transition to
the inactivated state, but I have
+

hyperkalemia it would never get

back to rest

wont get repolarization


They get LOCKED in the
inactivated STATE
Fast sodium channels remains
INACTIVATED

Decreased excitability
+
VOLTAGE-GATED CHANNELS

THEYR NOT FAST


THE END
Neuron
ACTION POTENTIAL

Subthreshold
Is the small stimulus that wont
get to Threshold
The magnitud of depolarization
depend upon the magnitud of
the stimulus
The stimulus can summate
The cell repolarize
+60- Depolarization is
Action potential - Threshold
+ CURVE
Repolarization The bigger stimulus will get to
+ CURVE threshold
When it get to threshold the fast
sodium channel opens so more
sodium channels will open and
cause more depolaritazion
Voltage-gated (fast) sodium
channels will produced the action
potential
HYPERPOLARIZATION The + conductance is higher
Em moves toward equilibrium for
+ , which is +60mV
When membrane potential
becomes positive it will inactivates THE ACTION POTENTIAL
the fast + channels
Resting potential: +
It doesnt close the + channels Despolarization: +
they are inactivated
Open fast + channels will
transition to the inactivated state
Now + conductance is LOW
The + channels will start to open
slowly, and + conductances start
rising
The cell membrane (Em) moves
toward equilibroum for + (-95mV)
thats why the cell hyperpolarizes
under Em -70mV (previous page)
1. The action potential is Pharmacology
all or none Blockes of the Voltage-gated
2. It cannot summate + channels
3. Regenerated so it 4-aminopyridine (A-AP)
conducts and is thus 3,4-Diaminopyridine (3,4-DAP)
propogated
Bird Poison
Period during which a
second potential can NOT
be produced
REFRACTORY PERIODS Result of opened or
inactivaed fast Na+
channels
Determines maximal
frecuency of action
potentials
A second action potential
but it has to be a higher
stimulus
Relative
Result of high +
conductances
Upstroke is
cause by Na+

Elevated
potassium
conductanes
NEURONS
Multiple Sclerosis (MS)
Conduction Velocity Demyelinating disease that can result in
Cell diameter conduction block
Big tube high velocity Spasticity and hyperrreflexia
Small tube less velocity Upper mottor neuron (UMN)
Myelination Guillain Barre (GB)
Demyelinating disease that can result in
Provides a higher velocity conduction block
Nodes of Ranvier generated a Flaccid paralysis
Saltatory conduction Lower mottor neuron (LMN)
NEUROMUSCULAR TRANSMISSION
Presynaptic membrane
Postsynaptic membrane Muscle cell
(Sarcolema)
The action potential gets generated to
the presynaptic terminal membrane
In the presynaptic the action potential
actives the Voltage-gated Ca2+
Channels
The Ca2+ opens by depolarization, the
calcium follows his electrical gradient
into the cell
NEUROMUSCULAR TRANSMISSION
The key STEP in synaptic transmission is the entry of calcium via voltage-
gated channels
The calcium inside the cell will cause the synaptic vesicle to release his
content
The amount of neurotransmitors release is directly related to the
concentration of calcium.
In the sarcolema is the Nicotinic receptor, which is a NON-selected Na+
K+ channel, so 3Na+ can come in and 2K+ can go out.
Na+ will cause DEPOLARIZATION called End Plate Potential (EPP) at
the neuromuscular junction
The action potential will spreads to the Voltage gated Na+ channel taking
the stimulus to threshold generating a multiple numbers of action potentials
Enzyme:
Acetylcholinesterase
It is an enzyme that
catalyzes the
chemical breakdown
of acetylcholina
Cholinergic

Non- Autonomic
Depolarizing Muscarinic Muscarinic
Depolarizing ganglia Nn
Nm Blockes antagonis agonists
Nm Blockers Blockers

Rocuronium Succinylcholine Hexamethonium Atropine Bethanecol

Atracuronium Mecamylamine Scopolamine Pilocarpine

Pancuronium
Excitability Symptons Alterations

Hypokalemia Hyperpolarizes
Ion Disturbances Chronic hyperkalemia Inactivated Na+ channels
Hypercalcemia Blocks Na+ Channels
Guillan-Barre Syndrome Conduction block
Loss of
ALS (amyotrophic lateral
Neurones/
sclerosis Loss of motor neurons
Demyelination
Aging
Weakness TTX
Decrease Hyporeflexia STX
excitability Paralysis Toxin/Drugs Block action potential
Sensory dficit Local anesthetics (caine drugs

Depolarizing NM blockers Succinylcholine


Rocuronium
Non-depolarizing NM Blockers Atracurium
Neuromuscular
Pancuronium
junction
(NMJ) Lambert-Eaton Reduce pre-synaptic Ca2+ channel
Myasthenia gravis (LMN) Block Nicotinic receptor
Botulium Prevents release of Acetylcholine (ACh)
Symptons Alterations Mechanism of action

Ion Disturbances

Acute hyperkalemia Depolarizes

Hypocalcemia Blocks Na+ channels


Loss of neurons/ Demyelination
Hyperreflexia
Multiple sclerosis (UMN) Conduction blocks
Spasms
INCREASED Muscle fasciculations
EXCITABILITY Toxins/Drugs
Tetany
Tremors Longer duration Action potential
CTX/BTX
Paresthesias + Channels stay in the OPEN STATE
Convulsions
4-AP/3,4-DAP Blocks Voltage-gated Ca2+ Channel

Neuromuscular junction (NMJ)

AchE inhibitors Acetylcholine last longer

Latrotoxin Inhibit the pre-synaptic Ca2+ channels


Phath/Pharm integration
Rocuronium
Non-Depolarizing NM Blocker Atracurium Decrease excitability
Pancuronium
Nicotinic (Ligand-gated ion channel) Increased excitability
Depolarizing NM blocker Succinylcholine
(initial effect)
Hexamethonium
Autonomic ganglia NN Blocker Mecamylamine
Atropine
Muscarinic (G-protein couple) Muscarinic antagonists
Scopolamine
Target tissues for parasympathetic post-
ganglionic neurons Bethanechol
Muscarinic agonist
Pilocarpine
Tetrodotoxin (TTX) Puffer fish
Blocks Voltage-gate Na+ Channel Increased Excitability
Saxitoxin (STX) Red tide algae
3,4 Diaminopyridine (3,4-DAP)
+ Channels stay in the OPEN STATE Decreased excitability
4-Aminopyridine (4-AP)
Prevents release of Acetylcholine (ACh) Botulinum toxin (Botox) Decreased excitability
AChE indirect inhibitors Physostigmine (Goes in the brain)
Increased Excitability
(Organophosphates) Neostigmine (Doesnt go in the brain)
Activates Voltage-gated Ca2+ Channel Latrotoxin opens up the Ca2+ channel Increased Excitability
Reduce ability of pre-synaptic Ca2+ channel Lambert Eaton sndrome autoimmune Increased Excitability
Block Nicotinic receptor Myasthenia Gravis autoinmune Increased excitability
SYNAPSIS BETWEEN NEURONS

EPSP:
Excitatory

IPSP:
Inhibitory

EPP: Nerve to
muscle
EPSP IPSP
Excitatory fire an action Inhibitory
potential Decreased excitability of the
postsynaptic neuron
Result of increasing Na+ Result of increasing Cl-
Receptor Receptor
Nicotinic (Ligands GABAa&c: GABA
Acetylcholine DRUGS: Benzodiazapines
Barbituates
Nm and Nn Glycine
Non-NMDA Inhibitory in the alfa motor neuron
Ligands: GLUTAMATE and Found in ventral horn of the spinal
cord
ASPARTATE
Tetanus toxin BLOCKS the
NMDA release of GLYCINE
Direct FLOW of CURRENT from cell to cell
This comunication occurs cia GAP JUNCTIONS
Cardiac cells and single smooth muscle have
these electrical synapsis
Its rapid bidirectional transmission
MUSCARINIC RECEPTORS IN PARASYMTHATICS
Alpha motor neuron

Receptor

Receptor

Receptor

Ach
Nicotinic
Receptor