Lecture 9: Membrane electrophysiology Flashcards
What is voltage (V)? What units is it measured in?
aka electric potential, electromotive force, or electrical potential difference
Voltage is the amount of work required to move a unit of charge between two points.
analogous to water pressure
Measured in joules/coulomb or volts (V).
What is current (I) in electrical systems?
the flow of electrons
How is current (I) measured?
In amperes
One ampere equals one coulomb of charge (or 6.24 x 1018 electrons) moving past a point in one second.
What is current (I) in biological systems?
current is carried by ions
analogous to the flow of water.
What is resistance (R)? How is it measured?
Resistance is the opposition to current in an electrical system.
It is measured in ohms and is defined as the ratio of voltage (V) across a resistor to the current (I) through the resistor
It is analogous to a restriction in the flow of water (for example, by crimping a hose)
What is conductance (G)?
Conductance is the inverse of resistance
It describes how readily ions or electrons can flow
What is Permeability?
The ability of a substance to permeate or flow (e.g. pass through a membrane)
What is Capacitance (C)? What is it measured in?
Capacitance is the ability of a body or device to store charge.
Capacitance is measured in farads.
A one farad capacitor will have a one volt difference across its plates when charged with one coulomb of charge.
Capacitors in biological systems
Biological membranes constitute significant capacitors
Parallel plate capacitor
In a parallel plate capacitor, the capacitance is proportional to the area of the plates and is inversely proportional to the distance between the plates.
Similar to a cell (lipid bilayer is capacitor)
See figure
Ohm’s law
Current (I) = Voltage (V)/ Resistance (R)
I=V/R
V=IR
R=V/I
How does K+ contribute to the RMP?
The concentration of K+ is much higher inside cells than outside.
The K+ permeability is quite high in resting cells (channels open)
Movement of K+ from the inside to outside of cells creates a negative environment within cells.
What is the primary conductance at rest?
Movement of K+
tends to dominate over other ion conductances
As such, K+ is the primary contributor to the resting membrane potential.
How can changes in K+ affect the RMP?
While the intracellular concentration of K+ tends to remain relatively stable, changes in extracellular K+ can occur and profoundly alter the resting membrane potential.
Conductance of Na+ at rest and upon excitation
At rest, the conductance to Na+ is typically very low.
Upon excitation/stimulation of the cell, the Na+ conductance can increase dramatically.
This occurs because Na+ channels open in response to some signal.
The Na+/K+ ATPase is responsible for maintaining these ion gradients.
Neuronal action potential and permeability to Na and K
Resting state: All gated Na+ and K+ channels are closed. No ions move
Depolarization: Voltage-gated Na+ channels open. Na+ flows into the cell
Threshold is reached (around -55 mV) and depol. becomes self-generating. Interior of cell becomes very positive and action potential is generated.
Repolarization: Na+ channels are inactivated and K+ channels open. K+ channels are slower, so decline is less steep than incline
Hyperpolarization: Some K+ channels remain open, Na+ channels reset
See figure
Cardiac action potential
Depolarization (Na+ into cell)
Slight repolarization: K+ begins to move out
Plateau: due to Ca 2+ entering the cell through slow channels. Works against K+
Repolarization: Ca 2+ channels deactivate and K+ channels are open
See figure
What does the equilibrium potential for an ion tell us?
The equilibrium potential for any given ion tells us the membrane potential at which the chemical and electrical forces would be exactly balanced.
Nernst equations
See figure
log(1) =
log(10) =
log(100) =
log(-10) =
log(1) = 0
log(10) = 1
log(100) = 2
log(-10) = -1
How many distinct ion channels are there in the human genome?
Over 200
Selectivity of ion channels
Typically, ion channels are highly selective for a single type of ion, although certain channels permit more than one type of ion to permeate.
What do ion channels allow ions to do?
flow down their concentration gradients.
What are ion channels characterized by?
ion permeability
gating
location in the body.
Ion transporters vs ion channels
Ion transporters are not ion channels as they do not have a simple pore allowing ions to flow down their concentration gradients.
Transport rate of ion transporters is slower than channels
Types of ion channels
Some only allow ions to pass down their concentration gradients by facilitated diffusion.
Other harness the energy in a different ion gradient to facilitate secondary active transport
Ion pumps utilize ATP to transport substances against their concentration gradient.
Ion pump example
The Na+/K+-ATPase
maintains the concentration gradients for Na+ and K+ in cells.
utilizes ATP to move these ions against their concentration gradient.
See figure
What inhibits the NA+/K+ ATPase?
Digoxin (orouabain) inhibits this pump.
What is an example of an ion counter-transporter?
The NA+-Ca2+ exchanger
Utilizes the energy in the Na+ gradient to move Ca2+ against its concentration gradient (out of cell)
See figure
Where is the Na+ - Ca2+ exchanger important?
This transporter is critical for cardiac muscle relaxation.
Ion symporter example
Na+ - glucose co-transporter
Na+-glucose transporters are co-transporters or symporters that facilitate the absorption or reabsorption of glucose in the intestine and gut.
When are Na+ - glucose co-transporters a target for drugs?
Type 2 diabetes.
Voltage gated channel example
Na+ channel
This channel opens in response to membrane
depolarization.
Shortly after activation, it inactivates.
This process is referred to as gating.
See figure
Three conformations of voltage gated ion channels
Open (pore is open, ball and chain are not blocking)
Closed (pore is closed)
Inactivated (ball and chain blocking)
See figure
When do voltage gated ion channels open?
inresponseto membrane depolarization.
Examples of voltage gated ion channels
Na+, Ca2+, and K+ channels.
What do defects in voltage gated ion channels cause?
widevariety of diseases including periodic paralyses, deafness, and sudden cardiac death.
What are ion channels targeted by?
Drugs
Toxins
Venoms
What causes opening of ligand gated ion channels
open in response to the binding of a chemical substance.
Where are ligand gated ion channels prominently expressed?
Neuromuscular junction
Action potentials in neurons vs cardiac cells
Neurons: 1-2 milliseconds
Cardiac cells: 300-400 milliseconds (heart needs time to fill with blood)
Frequencies in brain vs heart
Brain: 200 APs per second (200 Hz)
Heart: 1-3 Hz
Impact of axon diameter on conduction velocity
larger diameter fibre has less internal resistance, causing:
more current to flow down the axon flow (path of least resistance)
less decrement of current per unit length
longer length of fibre above threshold
therefore faster conduction velocity
What is myelin?
multilayered wrap of membrane around an axon formed by glia cells.
What cells form myelin?
“Schwann cells” in the peripheral nervous system
“Oligodendrocytes” in the CNS
How does myelination increase conduction velocity?
voltage gated Na+ and K+ channels are located in the small gaps between adjacent myelin wraps,
APs are created at these “Nodes of Ranvier”
action potentials skip ahead a few nodes at a time “jumps” from node to node. This increases conduction velocity enormously.
How does demyelination affect action potential?
demyelination strips away the myelin insulation and makes action potential propagation more precarious
propagation may slow, become intermittent, or fail.
Are peripheral nerves myelinated or unmyelinated?
They are a mix
How do local anaesthetics work?
Note: small diameter, unmyelinated fibres convey pain information from the periphery to the spinal cord.
LAs block conduction by reversibly preventing the opening of the voltage- gated Na+ channels responsible for the action potential.
given enough LA, conduction in all fibres, sensory and motor will cease.
small diameter fibres are more susceptible to block than larger fibres because of the
greater need in small fibres to depolarize adjacent membrane to propagate the AP.
therefore, pain sensation (small fibres) is blocked at a lower concentration of LA than fine touch or motor axons (large fibres)
What is analgesia?
relief of pain by altering perception of nociceptive stimuli without producing anesthesia or loss of consciousness.
What is anesthesia?
loss of sensation resulting from pharmacologic depression of nerve function or from neurological dysfunction.
What is the chronological order of the major events in synaptic transmission.
- Action potential
- terminal depolarization
- Ca2+ channels open
- Vesicles duse with pre-synaptic membrane and release neurotransmitter
- Receptor binding on the post-synaptic membrane by neurotransmitter
- Channels in the post-synaptic membrane open, produce post-synaptic potential
- Neurotransmitter is terminated in the synapse
- Reuptake and re-assembly of the neurotransmitter in the pre-synaptic neuronal
How can each step of synaptic transmission be blocked or affected?
- AP propagation
(demyelination, neuropathy) - Terminal depolarization
(presynaptic inhibition, physiologic control, drugs) - Ca2+ entry
(Ca+2 channel loss) - Transmitter release
(blocked by drug/poison) - Receptor binding (receptor loss, blocked by drug)
- Ion channels open
(genetic channel defect, blocked by poison) - Terminate transmitter action
(blocked by drug) - Transmitter reuptake
(blocked by drug)
How does cardiac excitation spread?
An action potential initiated at the SA node first spreads throughout both atria. Its spread is facilitated by the interatrial and internodal pathways.
The AV node is the only point where an action potential can spread from the atria to the ventricles.
From the AV node, the action potential spreads rapidly throughout the ventricles, hastened by a specialized ventricular conduction system consisting of the bundle of His and Purkinje fibers.
See figure
How do intracardiac defibrillators (ICD) work?
Atrial lead is passed through left subclavian vein, to the left atrium.
Defibrillation coil is in left ventricle
Subcutaneous lead is outside the body
See figure
Limb and chest leads
See figure
