Neuro-202 - Cellular and Molecular

Winter Quarter 2026

Unipolar Neuron

neuron with one axon extending from the soma, primarily found in invertebrates

Pseudounipolar Neuron

specialized sensory neurons with a single process extending from the soma and splitting into two branches, serving as both axon and dendrite. these neurons primarily transmit peripheral sensations like touch, pain, and proprioception to the central nervous system. located at the dorsal root ganglia and cranial nerve ganglia.

Bipolar Neuron

neuron with one dendrite and one axon extending from the soma

Multipolar Neuron

neuron with more than two neurites extending from the soma

Function of Motor Neurons

transmit electrochemical signals from the central nervous system (brain and spinal cord) to muscles and glands, enabling voluntary and involuntary movement

Function of Sensory Neurons

detect external and internal stimuli, such as light, sound, touch, temperature, and chemical changes, and convert them into electrical impulses to transmit to the central nervous system

Function of Interneurons

intermediate neurons that act as regulators to connect sensory and motor neurons, located in the brain and spinal cord (central nervous system). these neurons regulate excitatory firing, maintain balance via inhibition (oftentimes using GABA), and form circuits for memory and motor control

Glutamatergic Neurotransmitter (Glutamate)

primary excitatory neurotransmitter in the central nervous system, responsible for exciting neurons and causing them to fire action potentials. essential for neural plasticity, learning, and memory, acting on receptors such as NMDA and AMPA. excess is linked to seizures and neurodegenerative diseases like Alzheimer’s.

GABAergic Neurotransmitter (GABA)

primary inhibitory neurotransmitter in the nervous system that is synthesized directly from glutamate by the enzyme GAD. targets GABA A ion channels and G-Protein Coupled Receptors (GCPRs)

GAD converts glutamate to GABA

Dopaminergic Neurotransmitter (Dopamine)

modulatory neurotransmitter (neuromodulator) involved in reward, motivation, motor control, and executive function, and dysfunction in this system is heavily involved in Parkinson’s disease and addiction. can be both excitatory and inhibitory dependent on G-Protein Coupled Receptors (GCPRs)

Serotonergic Neurotransmitter (Serotonin)

modulates neural activity (neuromodulator) mostly thorugh G-Protein Coupled Receptors and one type of ion channel

Cholinergic Neurotransmitter (Acetylcholine)

ACh acts as both a neuromodulator and fast-acting neurotransmitter. can bind to nicotinic receptors, which are ionotropic ligand-gated ion channels to allow positive Na+ and Ca2+ influx (excitatory). can also bind to GPCRs, which are metabotropic and can be excitatory or inhibitory to depolarize or hyperpolarize cell potential

Ionotropic Receptors

ligand-gated ion channels that produce rapid, direct, and local neuronal responses by allowing ions to flow through the membrane

Metabotropic Receptors

G-protein coupled receptors (GCPRs) that act slower through intracellular signaling cascades, leading to longer-lasting and broader metabolic changes

Astrocytes

type of glial cells that regulate the chemical content of extracellular space (ions, neurotransmitters) and control the formation and stabilization of synapses. often located at synapses.

also connect soma of different neurons and dissipate extracellular K+ concentration through Potassium Spatial Buffering

Oligodendrocytes/Oligodendroglia cells

type of glial cells that create myelin to insulate axons and enable more efficient propagation of electrical signals down the axon. located in the central nervous system (CNS)

Schwann Cells

type of glial cells that create myelin to insulate axons and enable more efficient propagation of electrical signals down the axon. located in the peripheral nervous system (PNS)

Microglial Cells/Microglia

type of glial cells that are macrophages (immune response cells) of the central nervous system (CNS), which are responsible for inflammatory response and engulfing cellular debris, also prune away synapses

Ependymal Cells

type of glial cells that are responsible for the production and regulation of cerebrospinal fluid (CSF) and are involved in neuro-regeneration after injury (will see more in 206)

Selectivity

describes which ions can pass in the context of channels (e.g., non-selective cation channels, Na+ selective, Cl- selective)

Voltage-Gated Channels

ion channels that only open with certain voltage changes from membrane potentials

Ligand-Gated Channels

ion channels that are often located on the receptor side of synapses (post-synaptic) and open when they interact with neurotransmitters that bind to the active sites

Channels

• protein pore through the membrane

• bidirectional (ions can move in or out of the cell)

• direction of movement is determined by diffusion and electrical attraction/repulsion

• do not require energy (passive transport)

• can be specific to ion size/charge

• very fast, much faster than transporters

Transporters

• not an open pore

• change shape or conformation to move something from one side to the other

• bidirectional (ions can move in or out of the cell)

• direction of movement is determined by diffusion and electrical attraction/repulsion

• do not require energy (passive transport)

• can be specific to substrates

• slower than ion channels

• types: uniporters, symporters, and antiporters

Uniporter

transporter that moves one ion type at a time

Symporter

transporter that moves more than one ion type in the same direction (e.g., Na+ and K+ in one direction)

Antiporter

transporter that moves more than one ion type in opposite directions

Pump (ATPase)

• membrane protein that uses ATP as its energy source to concentrate something

• active transport

• pumps materials against its concentration gradient

Voltage (V)

the difference in electrical potential measured in Volts

Membrane Potential (Vm)

electrical potential difference (voltage) between the inside and outside of a cell

Resting Membrane Potential (Vrest)

Vm at rest, usually ~ -65 mV

Capacitance (C)

membrane’s ability to store charge, stored in farads

proportional to cell size (surface area)

inversely proportional to myelination (total membrane thickness)

Current (I)

movement of charge, measured in amps/amperes

Conductance (g)

how easily charges can move, measured in siemens, inversely related to resistance. proportional to permeability and the number of open channels

Resistance (R = 1/g)

how difficult it is for charges to move, measured in Ohms, inversely related to conductance

inversely proportional to the number of open ion channels

inversely proportional to cell size (number of leak channels and surface area)

inversely proportional to channel permeability (single-channel conductance)

How equilibrium potentials are established

when ion channels are originally introduced/opened, concentration gradient plays a larger role initially, so ions move down concentration gradient. then, to balance charge separation/difference, the ions will move back towards the original direction until equilibrium potential is established

Electrochemical Equilibrium (Eion)

reached when the electrical and diffusion forces are equal (and opposite) - a voltage with no net movement of ions. repulsion of like charges on the same side and the attraction of opposing charges pulls the ions back until E_K is reached

Concentration of Ions Inside and Outside Neurons

K+ higher inside; Na+, Ca2+, and Cl- higher outside

Nernst Equation

used to calculate voltage when the membrane is permeable to one type of ion

How permeability affects equilibrium voltage

more permeability means more movement and charge difference, so potential shifts in favor of ion with increased permeability (e.g., more Na+ channels open and increased Na+ permeability makes PNa+ > PK+, so potential shifts more positively in facor of Na+ and towards ENa.

Goldman Equation

used to calculate equilibrium voltage when the membrane is permeable to multiple types of ions

Potassium Spatial Buffering

how a network of astrocytes helps dissipate K+ ions across extracellular areas to prevent K+ overloading because Vrest is closer to E_K but more positive but K+ permeability is higher with more leak channels

Ohm’s Law

relates voltage, current (direction and amount), and resistance/conductance - V = I x R

Ionic Currents (I_ion), Driving Force, and Conductance

size and direction of ionic current is determined by the driving force and conductance (number of open channels)

I_ion = g_ion x (Vm - E_ion), in which the driving force is the difference between the membrane potential and equilibrium potential. when the driving force = 0 (no difference), there is no net ion movement.

Intracellular Electrophysiology Recording

experimentally introducing current and recording chances in membrane potential and activity of a neuron. differs from extracellular recording because the electrode is placed inside the neuron and can control/change the current input to measure one neuron’s response/changes in activity. (extracellular used for less invasive recording, more longitudinal/across multiple neurons)

Order/Mechanisms of Depolarization/Hyperpolarization

1) at synapse (source of current), presynaptic terminal releases neurotransmitters

2) neurotransmitters diffuse into the synaptic cleft and bind to receptors on the post-synaptic membrane. these are often ligand-gated ion channels, so binding to specific neurotransmitters opens the channels, allowing ions to flow through

3) positive inward or outward current (dependent on what is moving in/out) (e.g., Ca2+/K+ influx, Cl- outflux)

4) this makes the interior of the cell more positive/negative and the membrane potential more positive/negative, which is depolarization/hyperpolarization and can make it easier/harder for the neuron to fire action potentials

Current Clamp Recording

• control current input

• record Vm (membrane potential)

Optogenetics (Transgenics approach)

using light to introduce current into cells, which is easily reversible. often paired with intracellular electrophysiology recording to understand changes of function or activity in neurons based on excitation/inhibition

channelrhodopsin-2 non-selective cation channel responding to blue light, which causes depolarization (gain of function experiment)

halorhodopsin (Cl- pump) responding to yellow light, which moves negative charge from outside to inside and makes it harder to activate or depolarize the cell, which inhibits the function of the neuron (loss of function experiment)

Channelrhodopsin and Example

used in nonselective cation channels and opens in response to blue light, causing an inward positive current and depolarization in neurons

example: transgenic approach in which blue light laser impacted/promoted sleep vs wake. gain of function experiment in which different neurons exhibited different functions (one test resulted in promoting sleep after blue light laser with one neuron tested, and another test resulted in promoting wakefulness upon blue light laser in another neuron). measured muscle activity and brainwave activity monitoring in mice

Relationship between Soma Size and Current Input

smaller somas have fewer leak channels (low conductance, high resistance), and larger somas have larger surface areas with more leak channels (high conductance, low resistance). to achieve the same potential, the larger cell needs more current input because it is more leaky/conductive to experience the same voltage change as the smaller cell. this is because not all of the introduced current will contribute to membrane potential change, so smaller voltage change will be measured with the same current input.

Rate of Vm Change is inversely proportional to Time Constant

change in voltage at a given time is equal to the final voltage chance upon reaching the new steady state multiplied by (1-e^(-t/time constant)). when t = time constant, the voltage has risen 63% of its final (maximum) increase). time constant = resistance x capacitance.

voltage changes fastest when time constant is small

Action Potential

also known as a spike, impulse, or discharge. defined as a large and fast change in membrane potential that neurons use to transmit information

information is encoded in what types of neurons are firing action potentials, how many neurons are firing, and the frequency/pattern of action potentials within one neuron

Threshold

membrane potential at which a spike is generated

Sub-Threshold Potentials

“graded” or linear relationship described by Ohm’s Law. more current leads to larger depolarization

Parts of an Action Potential

depolarization segment:

starts at resting potential, then graded (sub-threshold) depolarization

upon reaching threshold, action potential begins with steep rising phase

when Vm >0, that is considered the overshoot, which includes the end of the rising phase and start of the falling phase, at which the Vm is closest to E_Na

repolarization segment:

steep falling phase

hyperpolarization segment:

undershoot when Vm < Vrest, at which the Vm is closest to E_K

returns to resting potential

Resting Membrane Potential (Vrest)

established by unequal ion concentrations across the cell membrane and selective ion permeability

at rest, P_K is much greater than P_Na due to more leak K+ channels than Na+ leak channels

Characteristics of the Rising Phase of an Action Potential

• positive input current causes membrane potential (Vm) to depolarize

• depolarization opens voltage-gated Na+ channels (Nav channels)

• Na+ permeability (PNa) becomes higher than K+ permeability (PK) leak channels alone, so inward Na+ current (from influx) > outward K+ current (from leak channels)

• Vm depolarizes further

• Na+ current brings Vm towards the Na+ equilibrium potential (E_Na)

• voltage-gated K+ channels (Kv channels) open slowly/gradually throughout the rising phase

• positive feedback loop: depolarizing causes Nav channels to open, which causes inward Na+ current to increase positive charge within the neuron and cause further depolarization

Characteristics of the Falling Phase of an Action Potential

• voltage-gated Na+ channels (Nav channels) inactivated, as they are time-dependent and have fast kinetics

• voltage-gated K+ channels (Kv channels) open gradually, as they have slow kinetics

• outward K+ current (through both Kv and leak K+ channels) > inward Na+ current/ion influx as more channels inactivate

• Vm repolarizes and returns to resting potential and then hyperpolarizes by becoming more negative than the resting potential because Kv channels are still open, but Nav channels are inactivated/closed

• K+ current brings Vm towards K+ equilibrium potential (EK)

Voltage-Clamp Technique

• indirectly measures current through voltage-gated channels

• intracellular electrophysiology experimentation, control membrane potential

1) measure membrane potential

2) compare Vm to desired (command) potential

3) when Vm and command potential differ, electrode injects or withdraws current from the neuron to maintain the command potential

• compensation current generates instantaneously and is equal to I_ion (current of ions from flowing in or out) but in the opposite direction

4) measure the compensatory current to indirectly measure I_ion through the voltage-gated channels

Characteristics of Depolarization-Elicited Na+ and K+ currents, Also How Toxins are used to Isolate Na+ and K+ currents (I_K and I_Na)

tetraethylammonium (TEA) blocks I_K by blocking channels, shows that Na+ current is negative (inward) in response to depolarization, has a short latency (small time delay) and a shorter duration

tetrodotoxin (TTX) blocks I_Na by blocking channels, shows that K+ current is positive (outward) in response to depolarization, has a long latency (larger time delay) and a longer duration

Voltage-Gated Na Channel (Nav)

• single polypeptide with four domains that form a pore in the cell membrane

• fast to open, fast to inactivate

• voltage sensitivity derives from S4 alpha helix

• Na+ selectivity derives from pore loop, which acts as a filter

• voltage-gated channels do not open all at once at a specific Vm, but the PROBABILITY of the channel opening increases as Vm increases

• blocking particle mediates inactivation

• channel inactivates after a short amount of time during depolarization, but there is no current flowing through because of the particle

• must wait until reaching the resting membrane potential before the blocking particle can move out and the channel can close and reset (de-inactivate)

• conformation change allows the channel to reset for another depolarization

• channel blockage/inactivation is important because of positive feedback loop: depolarization causes Na+ chnnels to open, which causes inward Na+ current (depolarization), so they are much more likely to open than Kv channels

Delayed Rectifier Voltage-Gated K Channel (Kv)

• four polypeptides form a pore

• voltage-gated, so channel is sensitive to change in voltage

• channels does not inactivate (no inactivation/blocking particle)

• slower kinetics, so the channels are slow to open and close

• responsible for the repolarization phase of the action potential

• current carried by these channels is referred to as I_K

• long lasting openings of K+ channels continues outward currents during the falling phase and makes membrane potential more negative

• less likely to open because of negative feedback loop: depolarization causes K+ channels to open, and outward K+ current causes repolarization

Whole-Cell Recording

whole-cell current clamp recording measures voltage while keeping current constant

whole-cell voltage clamp recording indirectly measures current by comparing flow across ion channels and comparing it to the command potential

Tonic Firing

neuron fires evenly-spaced single action potentials

Burst Firing

neuron fires brief, high-frequency clusters of action potentials separated by periods of inactivation/little or no activity in between

Significance of Firing Patterns of Neurons/Functions of Ion Channels

understanding firing patterns of neurons and how they transmit signals is important to better understand the nervous system and neurological diseases when the neurons don’t contribute to neural function as they’re supposed to

Patch-Clamp Menthod

• uses a microelectrode to fix the Vm and measure ionic currents across a singular ion channel

• isolates currents from single channels using voltage-clamp

• the seal on the glass pipette is so tight that an electric current cannot pass through the seal, only through the ion channels within the patch of the membrane

• can control ion concentration of surrounding solution to mimic extracellular fluid or innersolution to mimic cytosolic/intracellular fluid

Opening Probability of Ion Channels

based on experimental data/recording!! for voltage-gated channels in response to depolarization: opening probability of ion channels = time channel is open / total time of recording

Outcomes of BKCa Single Channel Recording (Patch-Clamp)

• BKCa = Big KCa channels

• large conductance calcium and voltage-activated potassium channels are dually activated by membrane depolarization and elevation of cytosolic Ca2+ ions (inside cell)

• deflections showed when one channel opens or when two or more channels opened simultaneously

Nav Channel Inactivation and Maximum Firing Rate

Nav channel inactivation limits the maximum firing rate and how soon the following action potential can be generated

during the absolute refractory period, most Nav channels are inactivated, so current is not allowed through to trigger another action potential

during the relative refractory period, some Nav channels are still inactivated, but some have been de-inactivated, so a larger depolarizing current is needed to generate an action potential compared to when all the Nav channels are de-inactivated

Half-Width

the width of an action potential at half its height, in seconds. used to determine the duration of an action potential

narrower action potentials allow higher frequency firing

broader action potentials limit firing frequency

Sequential Opening of Voltage-Gated Na+ and K+ channels generates the Action Potential

fast but brief Na+ conductance and opening of Nav channels causes membrane potential to become very positive until inactivation

slow but broader K+ conductance and opening of Kv channels causes membrane potential to decrease quickly during falling phase (in combination with leak K+ channels) to repolarize and hyperpolarize the membrane potential

Transient Outward (A-type) K+ channel

• selective to K+ ions

• voltage-gated, opens in response to depolarization

• low-threshold, so a small amount fo depolarization can trigger

• fast kinetics, so faster source of K+ efflux compared to delayed rectifier K+ channels

• inactivates, has a blocking/inactivation partcile, some channels are inactivated at Vrest

• current carried by these channels is referred to as I_A

• hyperpolarization recruits A-type K+ channels that are inactivated at rest, which results in delayed firing and fewer action potentials

Significance of Kv Channels’ Slow Kinetics

if Kv channels had fast kinetics, inward Na+ and outward K+ currents would compete at the same time (short latency). would cause delay in firing or an inability to reach threshold to fire action potentials at all

Low-Voltage-Activated (LVA) Ca2+ Channel

• selective to Ca2+ ions

• voltage-gated, requires small depolarization to trigger opening response/increase channel opening probability

• low-threshold, so a small amount of depolarization can trigger opening response

• fast kinetics

• inactivates, has a blocking particle, transient current (T-type, spends a long time in inactivation state, “temporary”), some channels are inactivated at rest

• current carried by Cav channels is called I_Ca

• hyperpolarization recruits T-type channels that are inactivated at rest, resulting in increased spiking. inward current and depolarization makes membrane potentials more positive, allowing T-type to open briefly. Ca2+ doesn’t respond very well to outward current

High-Voltage-Gated (HVA) Ca2+ Channel

• selective to Ca2+ ions

• voltage-gated, requires larger depolarization to trigger opening response/increase channel opening probability

• high threshold, so opens during action potentials (large depolarizations)

• fast kinetics, so opents quickly in response to current

• slowly inactivates, has a blocking particle, and has a long-lasting current (L-type)

• high frequency firing of action potentials can result in slowly increasing intracellular Ca2+ concentration, which is very important for triggering release of neurotransmitters in axons/target cells

Calcium-Gated K+ Channel/Ca2+-dependent Kv channels (KCa channels)

• selective to K+ ions

• voltage gated AND ligand-gated, needs depolarization and binding of intracellular Ca2+ ions to activate opening response

• slow kinetics, so slow to open and slow to close

• does not inactivate, so no blocking particle

• current carried by KCa channels is referred to as I_KCa

• neurons with HVA Ca2+ channels and KCa channels can show spike frequency adaptation (decreased firing rate over time)

Hyperpolarization-activated cyclic nucleotide-gated (HCN) Cation Channel

• non-selective cation channel

• need hyperpolarization AND cyclic nucleotides to activate (voltage-gated and ligand-gated by intracellular cyclic nucleotides (e.g., cAMP and cGMP))

• does not inactivate, so no inactivation/blocking particle

kinetics

• driving force for Na+ ions and Ca2+ ions is higher than for K+ ions around resting potentials because further from ECa and ENa, so current is inward

• current carried by these channels is referred to as I_H, indicating “mediated by HCN”

• HCN channels can excite a hyperpolarized neuron, resulting in intrinsic spiking (no input but rhythmic output)

• also called the “funny current” or I_f because of the following loop: when the membrane potential hyperpolarized, HCN channels open and let in positive ions, which increases the membrane potential (which is known as a pacemaker potential). eventually, this slow climb hits the ignition point/threshold for Nav or Cav channels to fire an action potential and repreat the cycle