Lec 11: Electrical Signals I Flashcards
Cell‐to‐cell communication is absolutely essential for
coordinating physiological functions in multicellular organisms
Cell‐to‐cell communication is also used by
single celled organisms to signal to other organisms (either “friends” or “foes”)
Several universal mechanisms of cellular regulation because
these mechanisms are shared by many types of organisms (since all organisms have a shared evolutionary history)
- Types of cellular communication: (3)
- Broadly broken down into 2 main classes:
- ) Direct cell‐to‐cell signaling (via direct contact)
- ) Local signaling
- ) Long‐distance signaling
- ) Chemical signals (Endocrine, paracrine, autocrine)
- ) Electrical signals (Action potentials, receptor potentials)
In animals, the _____ ______ utilizes electrical signals to: (3)
Nervous System
- ) Receive information from either within or outside the body (via various sensory receptors)
- Sensory or Afferent pathways
- Photoreceptors, tactile (mechano-) receptors, chemoreceptors (taste, smell, internal), thermoreceptor, electrical receptors - ) Integrate the sensory information [Processing]
- Central nervous system (CNS): Brain and Spinal Cord - ) Carry out a specific response
- Motor or Efferent pathways
- Activation of various effector organs (muscle, glands,…)
Withdrawal Reflex: simple neural circuit (3 Steps)
- ) Afferent (Sensory) Pathway (input)
- ) Integration (Processing)
- ) Efferent (Motor) Pathway (output)
2 main categories of cells in the Nervous System:
- ) Neurons
2. ) Glial cells
Neurons are…
Neurons have the capacity to…
Neurons are the…
- excitable
- generate and conduct an electrical signal – action potential)
- functional cells of the NS
3 functions of Neurons:
- ) Sensory (carry electrical signal to the CNS)
- ) Interneurons (mainly in the CNS)
- ) Motor (carry the electrical signal away from the CNS to an effector organ)
Glial cells function as…
& 4 types:
- Supporting cells
- Several types: astrocytes, oligodendrocytes, Schwann cells, microglia,…
Review Neuron Structure (Multipolar Neuron)!!!
& name 8 structures of the neuron:
Cell Body (soma) Dendrites Axon Axon Hillock Axoplasm Myelin Sheath (nodes of Ranvier) Terminal Branches Terminal Bulbs
4 types of neurons:
& how are they different?
Bipolar (Interneuron)
Unipolar (Sensory Neuron)
Multipolar (Motoneuron)
Pyrimidial Cell
different anatomically (histologically)
Membrane Potential abbreviations
(Vm or Em)
Membrane Potentials are the…
Due to…
- basic Electrochemical Properties of Cells
- an unequal distribution of ions across a cellular membrane each cell will have a Resting Membrane Potential (Vm or Em)
Vm =
the quantitative electrical difference across that membrane and is measured as a voltage difference across the membrane (measured in mV, inside with respect to the outside of the cell)
Resting Membrane Potential (Vm) results from…
essentially, is the…
- the separation of charged particles (ions) across the cell membrane.
- quantitative difference in charge particles inside vs outside.
Due to unequal charge distribution across the membrane:
Potential for ions to move across the membrane.
What is potential energy? In a relatable example
(a boulder resting on top of hill. It is not moving, but has the “potential energy” to do so if it is nudged off the edge – stored energy)
The membrane potential is…
measured in…
- stored (potential) electrical energy
- millivolts.
Resting Membrane potential in quotes
“the potential for electrical current flow”
electrical energy =
= electrical current flow = kinetic energy of charge particle movement.
Squids have
giant axons to stimulate muscles to contract to forcefully expel water and allow the squid to escape from its predators.
In neurons, the membrane potential is primarily determined by:
3 ions (Na+, K+, and Cl-) and negatively charged impermeable ions that reside in the cell
How are resting membrane potentials generated?
Due to combined effects: (4)
1.) Diffusion (of substances down a concentration gradient)
2.) Electroneutrality – when ions are in solution they are found in balanced sets (cation and anions), example: NaCl dissociates to Na+ + Cl- in solution
(The charged particles can be separated)
3.) Semipermeable nature of membranes
4.) Na+/K+ ATPase pump
Membrane potentials allow for
the generation of electrochemical gradients across the membrane
Electrical potential (voltage) =
= the potential tendency for a charged ion to flow across a membrane (potential energy)
Membrane Potential Example (Simplified Donnan Equilibrium)
The balance (at equilibrium) between the electrical and chemical differences (electrochemical gradient) across the membrane = equilibrium membrane potential (magnitude of the difference in voltage across the membrane – one side is more positive than the other side)
(Na+/K+ Pump (or ATPase))
1.) ATP transfers…
2.) __ Na+ are pumped out
__ K+ are pumped in
- ) This allows…
- ) Type of transport?
- ) An important aspect of the pump is that…
- ) The pump is
- ) Which type of ATP pump is this?
1.) energy (high energy phosphate bond) to the pump during transport (hence, ATPase).
2.) 3 Na+ are pumped out
2 K+ are pumped in
- ) the pump to transport Na+ and K + against their concentration gradients.
- ) Direct (Primary) active transport
- ) the affinity for Na+ and K+ changes during the cycle.
- ) “electrogenic”
- ) P class pump
(Steady State (Resting Potential))
Some ion…
Which pumps…
The Na/K pumps helps to…
- leakage occurs (Na+ and K+), countered by the Na/K pump
- 3 Na+ out and 2 K+ in for every ATP hydrolyzed.
- “maintain” the resting membrane potential
- K+ is more concetrated in…
- so it has a tendency to move…
- leaving behind…
- membrane potential becomes more…
- the cytosol
- out of the cell
- trapped anions
- negative
- Na+ is more concentrated in…
- so it has a tendency to move…
- as Na+ enter, they…
- membrane potential becomes more…
- the outside of the cell
- into the cell
- neutralize excess negative charge in the cytosol
- positive
- Cl- usually crosses the membrane together with…
- As Cl- enters the cell the membrane potential becomes more…
- a permeable cation (K+)
- negative
Can you quantify the Equilibrium Potential for any individual ion?
Yes, by using the equilibrium potential
The equilibrium potential for any ion is
the electrical potential difference that exactly counterbalances diffusion due to the concentration difference. Sometimes called the reversal potential.
In a multi ion system the equilibrium potential is also the
voltage difference across the membrane, when the membrane is permeable to only that ion.
Nernst Equation function
Calculates the equilibrium potential for each individual ion
Ex (or Vx) =
= equilibrium potential for ion X (voltage)
Nernst Equation =
Ex = (RT/ZxF)ln([X]o/[X]i)
Ex = equilibrium potential for ion X (voltage) R = gas constant T = temperature in kelvin Zx = ion valence F = Farraday constant X = ion o = outside i = inside
Simplified Nernst Equation =
(fro a monovalent cation @ 37*C)
and its measured in ___ not ____
Thus, for every 10 fold change in the gradient, there is a
Ex = (61.5)log([X]o/[X]i)
- mVolts not Volts
- 61.5 mV change in E (Equilibrium potential) for that ion
- Multiple ions contribute to the…
- Use the _____ ____ _____ ______ to calculate the steady-state membrane potential
- net resting membrane potential
- GHK (Goldman-Hodgkin-Katz) equation
The GHK (Goldman-Hodgkin-Katz) equation takes into consideration: (2) & review equation! (screenshot cuz too long lol)
- ) Multiple ions
2. ) Membrane permeabilities for each ion
The resting membrane potential:
Mammals =
Squid Giant Axon =
Skeletal Muscle =
Mammals = ~ -70 to -80 mV
Squid Giant Axon = ~ -60 to -70 mV
Skeletal Muscle = ~ -90 mV
- In this state, at rest, the membrane is said to be…
- This means…
- At rest, the membrane potential is close to…
- polarized.
- the cytosolic side is negative with respect to the extracellular side
- the Eq potentials for K+ and Cl-
(Additional Considerations)
- If the membrane permeability for a specific ion is increased, then the…
- If the membrane permeability for an ion is very high, the…
- Example:
- membrane potential will ‘move’ towards the Eq potential (Eion) for that ion
- GHK equation simplifies to the Nernst equation for that ion (the other ions become negligible).
- Ex: if we dramatically increased the membrane permeability to Na+, then the membrane potential would approach ENa+ (+64 mV) at equilibrium
Nernst (Vion) & GHK (Vm) graphical rep
screenshot
2 Electrical Events in neurons
- ) Graded Potentials
2. ) Action Potential
Graded Potentials =
- Not…
- Dissipates with…
= A transient electrical signal that occurs due to permeability changes across the membrane, that can be of varying magnitude
- not “all or none”
- distance along a membrane (and time)
Action Potential =
- Is…
- Does it dissipate with distance as it travels along a membrane?
= A transient electrical signal that occurs due to permeability changes across a membrane, that has a magnitude that is essentially invariable
- “All or none”
- NO
Review Graded and Action Potentials graphs
screenshot
In order for a change in membrane potential to occur (graded or action potential), there needs to be
a change in conductance (movement) of some ion (Na+, K+, Cl-, Ca2+) across the membrane.
Changes in ion conductance result from
changes in permeability for that ion.
Generally, ion permeability changes result from
the opening or closing of some ion channel.
(Ion channels)
The changes in membrane permeability that cause the electrical events (graded potentials and action potentials) result from
changes in ion channel conductance (i.e., the open or closed state of an ion channel)
Ion channels =
Integral membrane proteins (protein complexes) that form ion-conducting pores across the membrane. They are gated.
2 Types of gated ion channels:
- ) Ligand-gated: Will open in response to binding a specific ligand
- ) Voltage-gated: Will open in response to a change in membrane potential
Ion channels can be studied using
patch clamping (whole cell clamping)
(Voltage-gated Channels)
- are specific to…
- exhibit high
- due to
- Channels may have…
- What allows the channel to open or close?
- What transiently closes the channel (inactivate) and where?
- ions
- selectivity (“Selectivity Filter”)
- amino acid – ion interactions at the pore opening & the size of the central pore
- multiple gating mechanisms (gates that open and close)
- Voltage sensor domains
- Inactivation domains at a second site (multiple gates)
(Action Potential (AP))
- APs are…
- APs result from…
- The AP travels…
- rapid (5-6 ms), but large electrical depolarizations & repolarizations of the plasma membrane
- the opening & closing of voltage-gated Na+ and voltage-gated K+ channels.
- down the plasma (axonal) membrane via propagation (it essentially reforms at successive regions along the membrane)
Each AP occurs in a series of 3 phases:
In order for an AP to occur the membrane potential must reach a threshold voltage (potential)
- ) Depolarization (“rising”) –opening of Na+ channels
- ) Repolarization (“falling”) – opening of K+ channels
- ) Hyperpolarization (“undershoot”) - due to prolonged opening of K+ channels
- ) Depolarization =
- Becomes…
- Approaches…
= (rising) - opening of Na+ channels
- positive inside with respect to outside
- ENa+ (permeability for Na+ is very high)
- ) Repolarization =
- Inside…
- Towards…
= (“falling”) – opening of K+ channels
- returns to negative with respect to outside
- the EK+ and away from ENa+
- ) Hyperpolarization =
- Approaches…
= (“undershoot”) - due to prolonged opening of K+ channels
- EK+ (Permeability for K+ is very high)
The absolute refractory period is caused by
Na+ channel inactivation
Subthreshold depolarization =
- At rest, if small positive charges applied to the internal cell membrane (or a small influx of positive ions, like Na+)…
- Membrane potential will…
- therefore no
= depolarization does not reach threshold
- the cell will depolarize slightly, but due to the high K+ permeability (conductance), K+ will move out to quickly counter balance the incoming Na+.
- recover following small depolarizations (sub-threshold graded potentials)
- no AP
What does a Subthreshold depolarization look like?
a little bump where depolarization should start
If a depolarization reaches a specific threshold voltage (~ -40 mV; usually about 15-25 mV higher than the resting potential), then
many voltage-gated Na+ channels will open
(Depolarization/Rising Phase)
1.) Depolarization causes…
- ) and also causes a…
- ) As Na+ enters via the open channels, more…
- ) The membrane potential never…
- ) At this time (peak of the AP), the channels become…
- ) Resulting in…
- ) the voltage gated Na+ channels to open
- ) Huge increase in Na+ permeability (bringing positive charge into the cell)
- ) channels (in that region of membrane) are stimulated to open, positive-feedback (Hodgkin Cycle) → large depolarization
- ) quite reaches the ENa+, because other channels (K+) are opened before it reaches ENa+
- ) inactivated for several milliseconds
- ) Absolute refractory period – no stimulus is capable of causing another action potential (because the Na+ channels can’t be opened – they are inactivated)
Absolute refractory period =
= no stimulus is capable of causing another action potential (because the Na+ channels can’t be opened – they are inactivated)
3 main states of Na+ channel:
1.) Closed (rest)
2.) Open (depolarization)
3.) Inactivated (end of depolarization and during repolarization)
Changes from Inactivated to Closed (end of repolarization)
2 main gates of Na+ channel:
- ) Activation gate
2. ) Inactivation gate
Activation gate details: (4)
- Closed at rest
- Open during depolarization
- Open during repolarization
- Closes at end of repolarization
Inactivation gate details: (4)
- Open at rest
- Open during depolarization
- Closed during repolarization (absolute refractory period)
- Opens during end of repolarization and beginning of hyperpolarization (relative refractory period)
Memorize 2 main gates of Na+ channel table
screenshot
What causes the Na+ channel gates to open and close? (2)
- ) Initial depolarization to threshold causes:
- Activation gate to open quickly (channel is now open)
- Inactivation gate to swing closed slowly (~0.5 ms delay) (channel is now inactivated). Thus, for a very short time, both gates are open and Na+ can flow into the cell - ) Repolarization to ~ -40 to -80mV causes both gates to reset (“deinactivation”)
- Activation gate closes first
- Inactivation gate opens second
- Thus, the possibility for another AP is restored
(During Repolarization)
- Na+ channels are…
- Leading to…
- Voltage-gated K+ channels are…
- Efflux of…
- inactivated (not just closed)
- Absolute refractory period
- opened
- K+ repolarizes the membrane towards the resting membrane potential
(During Repolarization)
What causes the Voltage-gated K+ channels to open?
Achieve an open state at…
- Depolarization (but they open very slowly)
- ~ +30 mV
(Hyperpolarization)
- Occurs due to…
- The membrane approaches…
- Once the membrane approaches ~ -40 to -80 mV…
- This results in…
- Eventually…
- the elevated K+ conductance
- the EK+, which is below (more negative than) the resting potential (“undershoot”)
- some Na+ channels are returned to their resting state (“deinactivated”)
- Relative refractory period: An AP can occur, but it is more difficult due to the elevated K+ conductance
- K+ channels eventually close
(Return to resting membrane potential)
1.) Does not require…
- ) Only involves…
- ) Leaking of…
- ) Although there are large changes in membrane potential during the AP, there are only…
- ) In fact, even if the Na/K pump is completely inhibited with the inhibitor…
- ) the Na/K pump
- ) ionic movements and changes in gating status (i.e., permeability) of the voltage-gated Na+ and K+ channels
- ) some Na+ into the cell
- ) negligible changes in total ion concentrations inside and outside of the cell.
- ) ouabain, successive APs can continue for prolonged periods.
Review Changes in membrane conductance during the AP graph
plzzzzz screenshot
- An AP is what kind of event?
- If threshold is reached, then…
- But…
- an “all or nothing” event
- an AP will fire
- not during the absolute refractory period
- The refractory period prevents
- Therefore…
- Thus Channels are either…
- APs from occurring too close together in time
- APs cannot “summate” (cannot add together)
- open or closed/inactivated (“all or nothing”)
- An Action Potential is essentially a
- Thus, the electrical signal (AP) is moved from
- The electrical signal (AP) allows for
- signal that is carried from one part of a neuron to another (along the axon).
- one place to another along the axon.
- communication within the CNS and for communication between the CNS and the effector organs and sensory organs