Neuronal Physiology

Communication Throughout the Body

The body uses two main signaling systems to coordinate physiological functions: the nervous system and the endocrine system. The nervous system provides rapid, short-term communication, while the endocrine system can mediate both moderate and long-term responses.

• Nervous system: Fast, short-term signaling via electrical impulses and neurotransmitters.

• Endocrine system: Moderate speed, long- or short-term effects via hormones released into the bloodstream.

Membrane Potentials and Electrical Signaling

Changes in Membrane Potential (Vm)

Excitable tissues such as nerves and muscles can undergo rapid changes in their membrane potential (Vm), generating electrical signals essential for communication.

• Polarization: Any state where the membrane potential is not 0 mV.

• Resting Membrane Potential (Vrest): The baseline negative potential inside the cell, typically around -70 mV.

• Depolarization: Membrane potential becomes less negative (moves toward zero).

• Repolarization: Return to resting membrane potential after depolarization.

• Hyperpolarization: Membrane potential becomes more negative than the resting potential.

Mechanisms of Membrane Potential Changes

Electrical signals are generated by the movement of ions across the cell membrane through specific channels, altering the membrane's permeability.

• Depolarization: Influx of positive ions (e.g., Na+) into the cell.

• Hyperpolarization: Efflux of positive ions (e.g., K+) out of the cell.

Types of Membrane Potential Changes

Graded Potentials

Graded potentials are local changes in membrane potential whose magnitude depends on the strength of the stimulus. They are important for short-distance signaling within neurons.

• Local change: Occurs at the site of stimulation.

• Stimulus strength: Greater stimulus opens more ion channels, producing a larger potential change.

• Gated Na+ channels: Opening leads to depolarization.

• Loss of charge: Graded potentials decrease in strength as they spread from the point of origin due to current leak out of the cell.

Spreading of Graded Potentials

Graded potentials spread by local current flow, where positive ions move away from the depolarized region, causing adjacent areas to depolarize. This spread is bidirectional but diminishes with distance.

Action Potentials

Action potentials are rapid, all-or-none electrical signals that travel long distances along neurons. They are initiated when graded potentials depolarize the membrane to a threshold value.

• Threshold: Typically about -50 mV, or 20 mV above Vrest.

• All-or-none: Once threshold is reached, the same magnitude of action potential is produced every time.

• Phases: Rapid depolarization (up to +30 mV), repolarization, and often an overshoot (hyperpolarization).

Membrane Permeability and Ion Channels

Changes in membrane potential during action potentials are due to the opening and closing of voltage-gated ion channels.

• Voltage-gated Na+ channels: Have activation and inactivation gates, cycling through closed, open, and inactivated states.

• Voltage-gated K+ channels: Open more slowly and have a single gate.

Restoration of Ion Gradients: Na+/K+ Pump

After an action potential, the Na+/K+ ATPase pump restores the original ion concentration gradients by pumping Na+ out of and K+ into the cell.

Neurons and Nerve Conduction

Neuron Structure and Function

Neurons are the functional units of the nervous system, specialized for the conduction of electrical signals.

• Cell body: Contains the nucleus and metabolic machinery.

• Dendrites: Receive incoming signals (graded potentials).

• Axon: Conducts action potentials away from the cell body.

• Axon hillock: Site where action potentials are initiated due to high density of voltage-gated channels.

Nerve Conduction Mechanisms

Action potentials are conducted along axons by two main mechanisms:

• Contiguous conduction: Action potentials spread to adjacent regions of the axon in unmyelinated fibers.

• Saltatory conduction: In myelinated fibers, action potentials jump from node to node (nodes of Ranvier), greatly increasing conduction speed.

Refractory Periods

The refractory period ensures one-way propagation of action potentials and limits their frequency.

• Absolute refractory period: No new action potential can be generated due to inactivated Na+ channels.

• Relative refractory period: A stronger-than-normal stimulus can initiate another action potential as some K+ channels remain open.

Synaptic Transmission

Synapse Structure and Function

Synapses are specialized junctions where neurons communicate with other neurons, muscles, or glands. The presynaptic neuron releases neurotransmitters that bind to receptors on the postsynaptic cell, altering its membrane potential.

• Voltage-gated Ca2+ channels: Open at the axon terminal, triggering neurotransmitter release.

• Neurotransmitter (NT): Diffuses across the synaptic cleft and binds to postsynaptic receptors, opening specific ion channels.

• Graded response: Postsynaptic potential depends on the amount of NT released and receptor activation.

• NT removal: Rapidly cleared from the synaptic cleft to terminate the signal.

Excitatory and Inhibitory Synapses

Synaptic responses can be excitatory or inhibitory, depending on the type of ion channels opened in the postsynaptic membrane.

• Excitatory postsynaptic potential (EPSP): Depolarizes the neuron, usually by opening nonspecific cation channels (Na+ influx, K+ efflux).

• Inhibitory postsynaptic potential (IPSP): Hyperpolarizes the neuron, typically by increasing K+ permeability.

Grand Postsynaptic Potential and Summation

Multiple synaptic inputs are integrated at the postsynaptic neuron. Summation of EPSPs and IPSPs determines whether an action potential will be generated.

• Temporal summation: Two or more EPSPs from the same presynaptic neuron occur in rapid succession.

• Spatial summation: EPSPs from different presynaptic neurons occur simultaneously and combine.

• Cancellation: IPSPs can negate the effects of EPSPs.

Cell-to-Cell Communication

Types of Physiological Signals

Cells communicate using electrical and chemical signals. Chemical signals, or extracellular chemical messengers (ECMs), are the primary means of communication and act as ligands for target cell receptors.

• Specificity, affinity, competition, saturation: Properties of ligand-receptor interactions that determine cellular responses.

Local Communication

Local communication occurs through direct cell-to-cell contact or diffusion of chemical signals over short distances.

• Gap junctions: Cytoplasmic bridges for direct electrical and chemical communication.

• Contact-dependent signals: Require membrane-bound molecules on adjacent cells.

• Paracrine signals: Act on nearby cells.

• Autocrine signals: Act on the same cell that secreted them.

Long-Distance Communication

Long-distance communication involves hormones, neurotransmitters, and neurohormones, which can travel through the bloodstream or along neurons to reach distant targets.

• Hormones: Secreted by endocrine glands, travel in the blood to distant targets.

• Neurotransmitters: Released by neurons, act on adjacent cells.

• Neurohormones: Released by neurons into the blood, act on distant targets.

Signal Transduction and Membrane Receptors

Extracellular Chemical Messengers (ECMs)

ECMs can be classified by their source and the location of their effects: autocrine, paracrine, neurotransmitters, endocrine, and neurohormones. They initiate cellular responses by binding to specific membrane receptors.

Categories of Membrane Receptors

There are four main categories of membrane receptors, each triggering different intracellular responses:

• Receptor-channel: Ligand binding opens or closes the channel.

• G protein-coupled receptor: Ligand binding activates a G protein, which opens an ion channel or alters enzyme activity.

• Receptor-enzyme: Ligand binding activates an intracellular enzyme.

• Integrin receptor: Ligand binding alters the cytoskeleton.

Signal Transduction: Second Messenger Systems

Signal transduction involves converting an extracellular signal (first messenger) into an intracellular response (second messenger). This often involves cascades of activation steps and amplification of the signal.

• Second messengers: cAMP, Ca2+, and others mediate cellular responses such as ion channel gating, enzyme activation, and changes in gene expression.

• Cascades: Sequential activation of proteins amplifies the signal.

Major Second Messenger Pathways

• cAMP pathway: Ligand binds to G protein-coupled receptor → activates adenylyl cyclase → converts ATP to cAMP → activates protein kinase A (PKA) → phosphorylates target proteins.

• Calcium pathway: Ligand binds to G protein-coupled receptor → activates phospholipase C → splits PIP2 into DAG and IP3 → IP3 increases intracellular Ca2+ → Ca2+/calmodulin complex activates proteins.

Additional info: These mechanisms are fundamental to understanding how neurons and other excitable cells generate, conduct, and integrate electrical and chemical signals, forming the basis for nervous system function and intercellular communication.