Rucete ✏ Lehninger Principles of Biochemistry In a Nutshell
12.6 Gated Ion Channels
This chapter explains how excitable cells generate rapid electrical signals through gated ion channels. Changes in membrane potential allow neurons, muscle cells, secretory cells, and sensory cells to communicate quickly. Voltage-gated and ligand-gated ion channels are central to nerve conduction, muscle contraction, hormone secretion, learning, memory, and sensory transduction.
Excitable Cells
• Certain cells in multicellular organisms are excitable.
• Excitable cells can detect an external signal, convert it into an electrical signal, and pass it on.
• The electrical signal is a change in plasma membrane potential.
• These changes are produced by gated ion channels.
Major Roles of Excitable Cells
• Nerve conduction
• Muscle contraction
• Hormone secretion
• Sensory processes
• Learning and memory
Ion Channels Underlie Rapid Electrical Signaling
• Sensory cells, neurons, and myocytes depend on ion channels.
• Ion channels provide regulated pathways for movement of inorganic ions across the plasma membrane.
• Important ions include Na⁺, K⁺, Ca²⁺, and Cl⁻.
• Channels open or close in response to stimuli.
Types of Gated Ion Channels
• Ligand-gated channels open when a specific ligand binds.
• Example: neurotransmitter binding.
• Voltage-gated channels open when membrane potential changes.
• Some channels are influenced by both ligand and voltage.
Na⁺/K⁺ ATPase Creates Membrane Potential
• The Na⁺/K⁺ ATPase is electrogenic.
• It pumps 3 Na⁺ out of the cell for every 2 K⁺ moved into the cell.
• This creates a charge imbalance across the membrane.
• The inside of the cell becomes negative relative to the outside.
• Typical membrane potential is about −60 to −70 mV.
Ion Concentration Differences
• Inside the cell:
• K⁺ concentration is high.
• Na⁺ concentration is low.
• Ca²⁺ concentration is very low.
• Outside the cell:
• Na⁺ and Ca²⁺ concentrations are high.
• K⁺ concentration is lower than inside.
Electrochemical Potential
• Ion movement across membranes is determined by electrochemical potential.
• It has two components:
• Concentration gradient across the membrane.
• Electrical potential difference across the membrane.
Opening Na⁺ or Ca²⁺ Channels
• When Na⁺ or Ca²⁺ channels open, these ions tend to move into the cell.
• This inward positive charge causes depolarization.
Opening K⁺ Channels
• When K⁺ channels open, K⁺ tends to leave the cell.
• Although electrical forces pull K⁺ inward, the concentration gradient outward is stronger.
• K⁺ efflux makes the inside more negative.
• This causes hyperpolarization or repolarization.
Opening Cl⁻ Channels
• For Cl⁻, electrical forces may dominate.
• Movement of Cl⁻ can also influence membrane potential depending on conditions.
Only Small Ion Flux Is Needed
• A physiologically significant membrane potential change requires movement of only a tiny number of ions.
• Therefore signaling usually does not greatly change total Na⁺, K⁺, or Cl⁻ concentrations.
Special Role of Ca²⁺
• Intracellular Ca²⁺ concentration is normally extremely low.
• Small Ca²⁺ influx can significantly raise cytosolic Ca²⁺.
• Therefore Ca²⁺ can function as an intracellular second messenger.
Membrane Potential Depends on Open Channels
• The membrane potential at any moment depends on:
• Which channel types are open
• How many channels are open
• Their ion selectivity
Importance of Precise Timing
• Timed opening and closing of channels produces transient voltage changes.
• These voltage changes allow:
• Skeletal muscle contraction
• Heart beating
• Secretion from secretory cells
• Hormonal responses
Ion Channels in Non-Animal Organisms
• Ion channels are not limited to animals.
• They are also important in bacteria, protists, and plants responding to environmental signals.
Neuronal Signaling Overview
• Neurons transmit electrical impulses called action potentials.
• Signals move from the cell body through the axon to the synapse.
• At the synapse, neurotransmitters carry the signal to the next neuron or a muscle cell.
Voltage-Gated Channels Produce Action Potentials
• Initially, the presynaptic neuron membrane is polarized (inside negative).
• A rapid sequence of channel opening and closing creates a wave of depolarization.
• This traveling wave is the action potential.
Step 1: Na⁺ Channel Opening
• Voltage-gated Na⁺ channels open first.
• Na⁺ enters the cell.
• Local depolarization occurs.
• Adjacent Na⁺ channels then open.
• This propagates the signal along the axon.
Directionality of the Action Potential
• After opening, Na⁺ channels enter a brief refractory period.
• During this time they cannot immediately reopen.
• This prevents backward propagation.
• Therefore the signal moves in one direction.
Step 2: K⁺ Channel Opening
• Shortly after depolarization passes, voltage-gated K⁺ channels open.
• K⁺ exits the cell.
• The membrane repolarizes.
• The membrane is reset for the next action potential.
Action Potential Reaches the Axon Terminal
• When depolarization reaches the axon tip, voltage-gated Ca²⁺ channels open.
• Ca²⁺ enters the terminal.
Step 3: Neurotransmitter Release
• Increased intracellular Ca²⁺ triggers exocytosis of synaptic vesicles.
• Vesicles release neurotransmitter into the synaptic cleft.
• In this chapter, the example neurotransmitter is acetylcholine.
Step 4: Signal Crosses the Synapse
• Acetylcholine diffuses across the synaptic cleft.
• It binds receptors on the postsynaptic neuron or myocyte.
Step 5: Ligand-Gated Channel Opening
• Acetylcholine receptors are ligand-gated ion channels.
• When acetylcholine binds, the channel opens.
• Na⁺ and Ca²⁺ can enter through the channel.
• The postsynaptic membrane depolarizes.
Step 6: New Action Potential
• If depolarization reaches threshold, the postsynaptic cell generates its own action potential.
• The signal then continues through the neural circuit.
Two Ways Ion Channels Convey Signals
• By changing cytoplasmic ion concentration (especially Ca²⁺), which then acts as a second messenger.
• By changing membrane potential, which influences other voltage-sensitive proteins.
Ionotropic Receptors
• Some receptors are themselves ion channels.
• These are called ionotropic receptors.
• They differ from metabotropic receptors, which work through second messengers.
Acetylcholine Receptor
• The acetylcholine receptor is an ionotropic receptor.
• It is a cation channel.
• Binding of acetylcholine opens the channel.
• Na⁺ influx depolarizes the target cell.
Other Neurotransmitters with Ionotropic Receptors
• Serotonin
• Glutamate
• Glycine
• GABA (gamma-aminobutyric acid)
Effects of Different Neurotransmitters
• Serotonin and glutamate commonly open cation channels and depolarize cells.
• Glycine commonly opens Cl⁻ channels and tends to hyperpolarize cells.
• GABA receptors can also regulate ion channels.
Neural Integration
• A single neuron usually receives input from many other neurons.
• Some inputs are excitatory (depolarizing).
• Some are inhibitory (hyperpolarizing).
• The membrane potential reflects the sum of all inputs.
• The neuron fires only if net depolarization reaches threshold.
Second Messengers Also Regulate Channels
• Intracellular molecules can regulate ion channels.
• Examples include:
• cAMP
• cGMP
• Ca²⁺
• ATP
• Other signaling molecules
• These mechanisms are important in vision, smell, and taste.
Toxins Target Ion Channels
• Many potent natural toxins act on ion channels.
Examples of Neurotoxins
• Dendrotoxin (black mamba snake) blocks voltage-gated K⁺ channels.
• Tetrodotoxin (puffer fish) blocks voltage-gated Na⁺ channels.
• Cobrotoxin (cobra) disables acetylcholine receptor ion channels.
Why Ion Channels Are Ideal Toxin Targets
• Ion channels are extraordinary amplifiers.
• Opening one channel can allow flow of about 10 million ions per second.
• Only small numbers of channel proteins are needed in neurons.
• Therefore a small number of toxin molecules can strongly disrupt signaling.
• Enzymes involved in metabolism are usually present in much larger amounts, so they are less efficient toxin targets.
In a Nutshell
Gated ion channels allow excitable cells to rapidly convert stimuli into electrical signals. Voltage-gated Na⁺, K⁺, and Ca²⁺ channels generate action potentials and neurotransmitter release, while ligand-gated channels on target cells convert chemical signals back into electrical responses. Because ion channels strongly amplify tiny molecular events, they are central to nervous system function and common targets of deadly toxins.