Midterm study
Week 1:
1. Understanding Neurons' Electrical Charge and Key Terms
Neurons have a resting membrane potential of around 70 mV, due to differences in ion distribution across their membranes.
Polarization: Refers to this resting state, where the inside of the cell is negative relative to the outside.
Depolarization: A decrease in membrane potential, making the cell more positive (e.g., moving from -70 mV to a positive value).
Hyperpolarization: An increase in membrane potential, making the cell more negative than the resting state.
2. Ion Channels and Their Functions
Types of Ion Channels:
Voltage-Gated Channels: Open in response to changes in membrane potential. For example:
Na⁺ channels: Open during depolarization to allow Na⁺ influx.
K⁺ channels: Open during repolarization to allow K⁺ efflux.
Non-Gated Channels: Continuously open and maintain the resting membrane potential.
Chemically-Gated Channels: Open in response to neurotransmitter binding.
Mechanically-Gated Channels: Respond to physical changes like pressure or stretch.
Regulation: Channels are regulated by stimuli such as voltage changes, chemical signals, or mechanical forces.
3. Semi-Permeable Membrane
The membrane's selective permeability allows ions like Na⁺ and K⁺ to pass selectively.
This creates a charge difference across the membrane: K⁺ efflux makes the inside negative, while restricted Na⁺ entry maintains this negativity.
4. Equilibrium Potentials for Na⁺ and K⁺
Equilibrium potential is the voltage at which there is no net movement of a specific ion.
Using the Nernst equation, the equilibrium potential for:
K⁺ is approximately 90 mV.
Na⁺ is around +60 mV.
5. The Role of the Goldman-Hodgkin-Katz Equation
While individual equilibrium potentials describe single-ion behavior, the Goldman-Hodgkin-Katz equation incorporates the contributions of multiple ions and their permeabilities.
It calculates the resting membrane potential more accurately by considering the higher permeability of the membrane to K⁺ compared to Na⁺.
6. Na⁺/K⁺ Pump
This pump actively expels 3 Na⁺ ions for every 2 K⁺ ions imported.
It maintains the ion gradients essential for the resting membrane potential and uses ATP for energy.
7. Action Potential
Stimulus Effect: A stimulus reaching the 55 mV threshold initiates an action potential.
Phases:
Depolarization: Na⁺ channels open, Na⁺ influx makes the inside positive.
Repolarization: K⁺ channels open, and K⁺ exits the cell, restoring negativity.
Hyperpolarization: The membrane potential becomes more negative than the resting state before stabilizing.
Week 2:
1. Refractory Periods and Voltage-Gated Na⁺ Channels
Absolute Refractory Period: No action potential can occur because voltage-gated Na⁺ channels are inactivated. This ensures the action potential moves in one direction.
Relative Refractory Period: Action potential can occur with a stronger-than-normal stimulus because some Na⁺ channels have reset, but K⁺ channels are still open.
2. Electrotonic Current Flow
After an action potential is initiated, local currents flow passively (electrotonically) to depolarize adjacent regions of the neuron membrane, which helps propagate the signal.
3. Neuron Leakiness
Neurons are referred to as "leaky" because ion channels and membrane properties allow currents to dissipate. This limits the distance that electrotonic flow can travel and makes signal regeneration necessary.
4. Modes of Cell Communication
Electrical Signaling: Ion flow occurs directly between cells through gap junctions (e.g., in the heart).
Chemical Signaling: Neurotransmitters diffuse across the synaptic cleft and bind to receptors on the target cell.
5. Chemical Signals Between Cells
Cells use neurotransmitters, hormones, paracrine factors, and autocrine signals to communicate:
Neurotransmitters: Short-range signaling, e.g., at synapses (acetylcholine, dopamine).
Hormones: Long-range signaling via the bloodstream, e.g., insulin.
Paracrine Factors: Local signaling, e.g., nitric oxide.
Autocrine Signals: Signals that affect the cell that secreted them.
Week 3:
1. Structure and Types of Synapses
Synapses connect neurons to their targets and are broadly classified into two types:
Discrete Synapses:
Located at axonal terminals, also called terminal boutons.
Neurotransmitters are released only from specific areas (active zones).
Diffuse Synapses:
Axons have swellings called varicosities.
Neurotransmitters are released across active zones of varicosities.
2. Classes of Neurotransmitters
There are two main classes, based on molecular size:
Non-Peptide Transmitters:
Include small molecules like amino acids (GABA, glutamate) and amines (dopamine, serotonin).
Synthesized in the cytoplasm of the axon terminal.
Transported directly to vesicles.
Peptide Transmitters:
Larger molecules like substance P or endorphins.
Synthesized in the neuron's cell body.
Transported to the terminal via microtubules (using kinesin motor proteins).
3. Transmitter Release Mechanism
The release of neurotransmitters involves:
Action Potential Arrival: Depolarizes the presynaptic terminal.
Calcium Influx: Voltage-gated Ca²⁺ channels open, allowing Ca²⁺ to bind to synaptotagmin.
Vesicle Fusion: Synaptotagmin activates the SNARE complex, docking vesicles to the presynaptic membrane.
Exocytosis: Neurotransmitters are released into the synaptic cleft.
Role of Ca²⁺: Calcium regulates vesicle docking and neurotransmitter release; its availability is brief to prevent depletion of vesicles.
4. Post-Synaptic Voltage Changes
Neurotransmitters evoke two types of changes:
Excitatory Post-Synaptic Potentials (EPSPs):
Depolarize the post-synaptic cell by allowing Na⁺ entry or K⁺ retention.
Inhibitory Post-Synaptic Potentials (IPSPs):
Hyperpolarize the post-synaptic cell by enabling Cl⁻ entry or K⁺ exit.
5. Termination of Neurotransmitter Action
The actions of neurotransmitters are terminated through:
Reuptake/Uptake:
Reabsorption into the presynaptic terminal or adjacent glial cells.
Enzymatic Degradation:
Enzymes in the synaptic cleft or post-synaptic membrane break down the neurotransmitter.
Diffusion:
Neurotransmitters diffuse away from the synaptic cleft.
Week 4:
Learning Objectives and Responses
1. Structure and Types of Synapses
Synaptic transmission involves convergence and divergence:
Convergence: Multiple neurons innervate a single post-synaptic neuron.
Divergence: A single neuron branches to innervate multiple post-synaptic neurons.
2. Neurotransmitter Binding and Receptor Types
Mechanisms of neurotransmitter action:
Neurotransmitters bind to receptors, which can:
Form ion channels (transmitter-gated ion channels), leading to membrane potential changes.
Activate G-proteins, which may indirectly alter membrane potential.
Activate second messengers that further modulate cellular responses.
Transmitter-Gated Ion Channels:
Excitatory channels cause depolarization by Na⁺ influx and K⁺ efflux.
Inhibitory channels cause hyperpolarization by Cl⁻ influx and K⁺ efflux.
3. Fast and Slow Synaptic Transmission
Synaptic inputs can occur at different speeds:
Fast Synaptic Transmission (<5 ms): Involves direct ion channel opening.
Slow Synaptic Transmission (20–200 s): Involves second messengers or longer-lasting changes.
4. Post-Synaptic Potentials and Action Potentials
Excitatory Post-Synaptic Potential (EPSP): Depolarization moves the membrane potential closer to the threshold.
Inhibitory Post-Synaptic Potential (IPSP): Hyperpolarization moves the membrane potential further from the threshold.
Post-synaptic potentials:
Graded responses: Decay with distance and vary in amplitude.
Can sum (e.g., via spatial or temporal summation).
Action potentials:
All-or-none responses: Do not decay over distance and cannot sum due to refractory periods.
5. Factors Influencing Synaptic Effectiveness
Location:
Synapses closer to the axon hillock are more effective in influencing action potential generation.
Pre-Synaptic Activity:
Depolarization size and duration in the pre-synaptic terminal affect neurotransmitter release and post-synaptic response.
History of Synaptic Activity:
Synaptic transmission can adapt based on previous activity, e.g., post-tetanic potentiation or depression.
Post-Synaptic Adaptation:
Post-synaptic neurons can regulate their responses to maintain balance.