Molecular Neuroscience II
Molecular Neuroscience Overview
Focus on molecules that regulate and control excitation and inhibition in the nervous system.
Electrical activity in the brain is essential for understanding practical measurements.
Emphasizes the importance of understanding molecular operations underlying observed phenomena in practicals.
Resting Membrane Potential
Sodium-Potassium ATPase: Pumps 3 sodium ions out and 2 potassium ions in, creating uneven ion distribution.
Resting membrane potential is largely maintained by the leaky flux of potassium ions (positive charged ions) from inside to outside, leaving a net negative charge inside the cell.
Concentration details in mammalian neurons:
Sodium: 142 mM (outside) vs. 10 mM (inside)
Potassium: Inverse distribution with more inside.
Chloride (Cl-): Higher outside than inside; influx reduces neuronal excitability.
Calcium's Role
Calcium ions (Ca2+) are present in much lower concentrations inside (1-2 mM) than outside (2 mM).
The significant diffusion gradient promotes Ca2+ influx, crucial for various cellular processes.
Essential to control intracellular calcium levels to prevent pathological consequences.
Neuronal Excitation and Inhibition
To excite a neuron: open channels that allow positive ions to influx.
To inhibit a neuron: can either bring in negative charges (like Cl-) or allow positive charges to exit (like K+).
Action potentials are driven by these ionic movements across the membrane through specific ion channels.
Intercellular Communication
Electrical Synapses
Gap Junctions: Allow direct electrical connections between adjacent neurons, facilitating rapid communication.
Important for synchronization of neuronal activity, especially in invertebrates.
Chemical Synapses
Characterized by a small gap (30 nm) between pre- and postsynaptic neurons.
Involves neurotransmitter release from presynaptic vesicles, binding to postsynaptic receptors influencing downstream electrical activity.
Synaptic Vesicles: Contain neurotransmitters; released through exocytosis triggered by calcium influx.
Communication involves complex enzymatic reactions, receptor interactions, and neurotransmitter dynamics.
Mechanism of Neurotransmission
Presynaptic Action Potential: Triggers the opening of voltage-gated Na+ and K+ channels.
Calcium Channels: Recognize depolarization and allow Ca2+ influx, critical for neurotransmitter release.
Calcium-Sensing Proteins (e.g., Synaptic Tag): React to calcium influx, facilitating membrane fusion of vesicles containing neurotransmitters.
Ion Channel Receptors: Postsynaptic receptors can be voltage-gated or ligand-gated and dictate whether the signal is excitatory or inhibitory.
Excitatory Response: When cations flow in and depolarize the membrane.
Inhibitory Response: When anions like Cl- flow in and hyperpolarize the membrane.
Feedback Mechanisms
Reuptake: Transporters on presynaptic cells or surrounding glia take neurotransmitters back into the cell, effectively terminating the signal.
Important for recycling neurotransmitters and ensuring proper neural communication.
Dependence on vesicle availability to ensure neurotransmitter release is efficient and regulated.
Key Concepts
Understand the actions of sodium (Na+), potassium (K+), and calcium (Ca2+) in bringing about excitability in neurons.
Familiarity with the distinction between electrical and chemical synapses enhances understanding of neural circuits and functions.
Integration of molecular mechanisms in neurotransmission is crucial for overall brain functionality, influencing behaviours and interactions.