5. Voltage-Gated Ion Channels part 1

Intrinsic Excitability

The ability of neurons to generate electrical signals due to maintaining precise electrochemical gradients of ions across their plasma membrane, establishing a resting membrane potential.

Nernst equation

A formula (E{ion} = rac{RT}{zF}ln rac{[ion]}{[ion]{in}}) used to calculate the equilibrium potential for a single ion across a membrane.

Goldman-Hodgkin-Katz equation

A more comprehensive equation than the Nernst equation, used to calculate the resting membrane potential by considering the permeabilities of multiple ions.

Current Clamp

An electrophysiological technique that involves injecting a controlled current into a neuron and measuring the resulting changes in membrane potential to observe natural responses like action potentials and synaptic potentials.

Voltage Clamp

An electrophysiological technique that actively controls the membrane potential of a neuron at a desired level and measures the ionic currents flowing across the membrane required to maintain that voltage, used to characterize specific ion channels.

Action Potentials

Rapid and transient 'all-or-none' changes in membrane potential that are the fundamental unit of information transmission in the nervous system, generated once the membrane potential reaches a threshold.

Depolarization (Rising Phase)

The phase of an action potential characterized by the rapid influx of Na^+ through voltage-gated sodium channels, driving the membrane potential positive.

Repolarization (Falling Phase)

The phase of an action potential characterized by the inactivation of voltage-gated sodium channels and efflux of K^+ through voltage-gated potassium channels, returning the membrane potential to negative values.

Hyperpolarization (Undershoot)

A transient period in an action potential where K^+ channels remain open, causing the membrane potential to become more negative than the resting potential.

Absolute Refractory Period

A period following an action potential during which no new action potential can be generated due to Na^+ channel inactivation, ensuring unidirectional propagation.

Relative Refractory Period

A period following an action potential during which a stronger-than-normal stimulus is required to elicit a new action potential, due to persistent K^+ efflux and some Na^+ channels recovering from inactivation.

Structure-Function Principle

The fundamental tenet that the specific sequence of amino acids (primary structure) of a protein directly determines its three-dimensional architecture and, consequently, its specific function, exemplified by ion channels.

Voltage-Gated Sodium Channels (Na_V)

Ion channels primarily responsible for the rapid depolarization phase of action potentials, mediating their initiation and propagation through rapid Na^+ influx, and characterized by fast activation and rapid inactivation.

Saltatory Conduction

The propagation of action potentials in myelinated axons where action potentials 'jump' between Nodes of Ranvier, greatly increasing conduction velocity.

Voltage-Gated Potassium Channels (K_V)

A diverse family of ion channels crucial for the repolarizing phase of action potentials, activating more slowly than Na_V channels and contributing to the return of the membrane potential to its resting negative state.

Delayed Rectifier KV Channels

A subtype of KV channels (e.g., KV1, KV2 families) that open with a delay during depolarization and are primarily responsible for the repolarization of action potentials.

A-type KV Channels

A subtype of KV channels (e.g., KV3, KV4 families) that activate and inactivate rapidly at subthreshold depolarizations, delaying the onset of subsequent action potentials and contributing to spike frequency adaptation.

Voltage-Gated Calcium Channels (Ca_V)

Ion channels that primarily allow the influx of Ca^{2+} ions, acting as a versatile intracellular second messenger to link electrical activity to biochemical events, such as neurotransmitter release.

Excitation-Secretion Coupling

The process at presynaptic nerve terminals where Ca^{2+} influx through Ca_V channels triggers the fusion of synaptic vesicles with the presynaptic membrane, leading to neurotransmitter release.

L-type (Ca_V1) Channels

"Long-lasting" voltage-gated calcium channels that require strong depolarization to open, crucial for muscle contraction, gene transcription, and synaptic plasticity in neurons.

T-type (Ca_V3) Channels

"Transient" voltage-gated calcium channels that activate at relatively low thresholds, often associated with pacemaker activity and rhythmic burst firing in some neurons.

TRP (Transient Receptor Potential) Channels

A large and diverse family of ion channels known for polymodal activation by various stimuli including temperature, chemical ligands, mechanical stretch, osmolality, and pH, beyond just voltage.

TRPV1 (Vanilloid Receptor 1)

A TRP channel activated by noxious heat (>43^ ext{o}C), capsaicin, and low pH, serving as a key mediator of inflammatory pain.

TRPM8 (Melastatin 8)

A TRP channel activated by moderate cold (<25^ ext{o}C) and cooling compounds like menthol, contributing to the sensation of coolness.

TRPA1 (Ankyrin 1)

A TRP channel activated by noxious cold (<17^ ext{o}C), irritating chemicals, and mechanical stimuli, playing a role in inflammatory and neuropathic pain.

Intrinsic Excitability

The ability of neurons to generate electrical signals due to maintaining precise electrochemical gradients of ions across their plasma membrane, establishing a resting membrane potential.

Nernst equation

A formula (E{ion} =\frac{RT}{zF}ln\frac{[ion]{out}}{[ion]_{in}}) used to calculate the equilibrium potential for a single ion across a membrane.

Goldman-Hodgkin-Katz equation

A more comprehensive equation than the Nernst equation, used to calculate the resting membrane potential by considering the permeabilities of multiple ions.

Current Clamp

An electrophysiological technique that involves injecting a controlled current into a neuron and measuring the resulting changes in membrane potential to observe natural responses like action potentials and synaptic potentials.

Voltage Clamp

An electrophysiological technique that actively controls the membrane potential of a neuron at a desired level and measures the ionic currents flowing across the membrane required to maintain that voltage, used to characterize specific ion channels.

Action Potentials

Rapid and transient 'all-or-none' changes in membrane potential that are the fundamental unit of information transmission in the nervous system, generated once the membrane potential reaches a threshold.

Depolarization (Rising Phase)

The phase of an action potential characterized by the rapid influx of Na^+ through voltage-gated sodium channels, driving the membrane potential positive.

Repolarization (Falling Phase)

The phase of an action potential characterized by the inactivation of voltage-gated sodium channels and efflux of K^+ through voltage-gated potassium channels, returning the membrane potential to negative values.

Hyperpolarization (Undershoot)

A transient period in an action potential where K^+ channels remain open, causing the membrane potential to become more negative than the resting potential.

Absolute Refractory Period

A period following an action potential during which no new action potential can be generated due to Na^+ channel inactivation, ensuring unidirectional propagation.

Relative Refractory Period

A period following an action potential during which a stronger-than-normal stimulus is required to elicit a new action potential, due to persistent K^+ efflux and some Na^+ channels recovering from inactivation.

Structure-Function Principle

The fundamental tenet that the specific sequence of amino acids (primary structure) of a protein directly determines its three-dimensional architecture and, consequently, its specific function, exemplified by ion channels.

Voltage-Gated Sodium Channels (Na_V)

Ion channels primarily responsible for the rapid depolarization phase of action potentials, mediating their initiation and propagation through rapid Na^+ influx, and characterized by fast activation and rapid inactivation.

Saltatory Conduction

The propagation of action potentials in myelinated axons where action potentials 'jump' between Nodes of Ranvier, greatly increasing conduction velocity.

Voltage-Gated Potassium Channels (K_V)

A diverse family of ion channels crucial for the repolarizing phase of action potentials, activating more slowly than Na_V channels and contributing to the return of the membrane potential to its resting negative state.

Delayed Rectifier KV Channels

A subtype of KV channels (e.g., KV1, KV2 families) that open with a delay during depolarization and are primarily responsible for the repolarization of action potentials.

A-type KV Channels

A subtype of KV channels (e.g., KV3, KV4 families) that activate and inactivate rapidly at subthreshold depolarizations, delaying the onset of subsequent action potentials and contributing to spike frequency adaptation.

Voltage-Gated Calcium Channels (Ca_V)

Ion channels that primarily allow the influx of Ca^{2+} ions, acting as a versatile intracellular second messenger to link electrical activity to biochemical events, such as neurotransmitter release.

Excitation-Secretion Coupling

The process at presynaptic nerve terminals where Ca^{2+} influx through Ca_V channels triggers the fusion of synaptic vesicles with the presynaptic membrane, leading to neurotransmitter release.

L-type (Ca_V1) Channels

'Long-lasting' voltage-gated calcium channels that require strong depolarization to open, crucial for muscle contraction, gene transcription, and synaptic plasticity in neurons.

T-type (Ca_V3) Channels

'Transient' voltage-gated calcium channels that activate at relatively low thresholds, often associated with pacemaker activity and rhythmic burst firing in some neurons.

TRP (Transient Receptor Potential) Channels

A large and diverse family of ion channels known for polymodal activation by various stimuli including temperature, chemical ligands, mechanical stretch, osmolality, and pH, beyond just voltage.

TRPV1 (Vanilloid Receptor 1)

A TRP channel activated by noxious heat (>43^\text{o}C), capsaicin, and low pH, serving as a key mediator of inflammatory pain.

TRPM8 (Melastatin 8)

A TRP channel activated by moderate cold (<25^\text{o}C) and cooling compounds like menthol, contributing to the sensation of coolness.

TRPA1 (Ankyrin 1)

A TRP channel activated by noxious cold (<17^\text{o}C), irritating chemicals, and mechanical stimuli, playing a role in inflammatory and neuropathic pain.

What factors does the Nernst equation take into account when calculating the equilibrium potential for a single ion?

The Nernst equation considers the gas constant (R), absolute temperature (T), the valence of the ion (z), Faraday's constant (F), and the ion's concentrations inside ([ion]{in}) and outside ([ion]{out}) the cell membrane.

What is the defining characteristic that categorizes action potentials as 'all-or-none' events?

Action potentials are 'all-or-none' because once the membrane potential reaches a threshold, a full-amplitude action potential is generated regardless of the stimulus strength, or none is generated at all.

What mechanism ensures the unidirectional propagation of action potentials along an axon?

The absolute refractory period, caused by the inactivation of Na^+ channels after an action potential, prevents the immediate re-firing of the same segment of the axon, thereby ensuring unidirectional propagation.

How do A-type KV Channels contribute to spike frequency adaptation in neurons?

A-type KV channels, which activate and inactivate rapidly at subthreshold depolarizations, delay the onset of subsequent action potentials, thus contributing to a decrease in firing rate over time, known as spike frequency adaptation.

Upon what principle does the Goldman-Hodgkin-Katz equation improve upon the Nernst equation for calculating resting membrane potential?

The Goldman-Hodgkin-Katz equation improves upon the Nernst equation by considering the relative permeabilities of multiple ions (e.g., Na^+ , K^+ , Cl^-), providing a more accurate calculation for the resting membrane potential of a cell.

What is the role of Voltage-Gated Calcium Channels (Ca_V) in linking electrical activity to biochemical events?

Ca_V channels allow Ca^{2+} influx, which then acts as a versatile intracellular second messenger, triggering a variety of biochemical events such as neurotransmitter release, gene transcription, and synaptic plasticity.

What are some of the diverse stimuli that can activate TRP (Transient Receptor Potential) Channels, beyond just voltage?

TRP channels are known for polymodal activation by stimuli including temperature (hot/cold), chemical ligands (e.g., capsaicin, menthol), mechanical stretch, osmolality, and pH.