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What is the purpose of cell communication?
To coordinate the activities of different cells and maintain homeostasis in the body.
How do cells communicate directly?
Through gap junctions that connect the cytoplasm of adjacent cells and allow ions and small molecules to pass freely.
What are gap junctions made of?
Connexons formed by six connexin protein subunits that create a channel between two cells.
What can pass through a gap junction?
Ions, metabolites, and signaling molecules smaller than approximately 1 kDa.
Why are gap junctions important in cardiac and smooth muscle?
They enable direct electrical coupling that allows simultaneous contraction by sharing ionic current between cells.
What is chemical or indirect communication?
The release of a chemical messenger by one cell that binds to receptors on another cell to produce a response.
What are the main classes of chemical messengers?
Paracrine factors, neurotransmitters, hormones, and neurohormones.
What determines whether a cell can respond to a particular messenger?
The presence of the specific receptor protein for that messenger.
What happens when a chemical messenger binds to a receptor?
It activates signal transduction pathways that lead to a functional response in the target cell.
What are the three main stages of cell signaling?
Reception, transduction, and response.
What happens during the reception stage?
The signaling molecule binds specifically to a receptor protein either on the cell membrane or inside the cell.
What happens during the transduction stage?
The receptor undergoes a conformational change that activates intracellular signaling cascades involving second messengers and enzymes.
What happens during the response stage?
The transduced signal leads to a specific change in cellular activity such as enzyme activation, secretion, or gene expression.
What are the two main categories of chemical messengers based on solubility?
Lipophilic (lipid-soluble) and lipophobic (water-soluble) messengers.
How do lipophilic messengers act?
They diffuse across the lipid bilayer and bind to intracellular receptors that regulate gene transcription.
How do lipophobic messengers act?
They cannot cross the plasma membrane and bind to surface receptors that trigger signal transduction pathways through second messengers.
Give examples of lipophilic messengers.
Steroid hormones such as cortisol, testosterone, and estrogen, thyroid hormones, and nitric oxide.
Give examples of lipophobic messengers.
Peptide hormones such as insulin and glucagon, and neurotransmitters like acetylcholine and norepinephrine.
Which type of communication is fastest?
Neural and electrical signaling through gap junctions or synapses.
Which type of communication is slowest but longest lasting?
Endocrine or hormonal communication.
What is autocrine signaling?
A cell releases a chemical messenger that acts on receptors on the same cell that secreted it.
What is paracrine signaling?
A cell secretes local chemical messengers that diffuse through the extracellular fluid to nearby target cells.
What is endocrine signaling?
Endocrine cells secrete hormones into the bloodstream to reach distant target cells.
What is synaptic signaling?
Neurons release neurotransmitters across synaptic clefts to receptors on postsynaptic cells.
What is neuroendocrine signaling?
Neurons release neurohormones into the blood which then act on distant target cells.
What determines the duration of response in a signaling event?
The type of chemical messenger, receptor dynamics, and rate of degradation or removal of the signal.
What are examples of fast, short-lasting signals?
Neurotransmitter signals at synapses that are rapidly degraded or removed.
What are examples of slow, long-lasting signals?
Endocrine hormone signals that circulate in the bloodstream for extended periods.
What type of receptors do lipophobic messengers bind to?
Integral membrane receptors exposed on the extracellular surface.
What type of receptors do lipophilic messengers bind to?
Intracellular receptors in the cytoplasm or nucleus.
What are the main types of plasma membrane receptors?
Ligand-gated ion channels, G-protein-coupled receptors, and enzyme-linked receptors.
What are ligand-gated ion channels?
Receptors that open an ion channel when a specific ligand binds, allowing ion flow that changes the membrane potential.
What is another name for ligand-gated ion channels?
Ionotropic receptors.
What happens when an ionotropic receptor is activated?
It changes conformation to open or close the ion channel, directly altering ion permeability and membrane voltage.
What are examples of ionotropic receptors?
Nicotinic acetylcholine receptor and GABA_A receptor.
What are G-protein-coupled receptors?
Receptors that interact with intracellular G-proteins when activated by a ligand to trigger second messenger cascades.
What is another name for G-protein-coupled receptors?
Metabotropic receptors.
What are G-proteins composed of?
Three subunits: alpha, beta, and gamma.
What happens when a ligand binds to a GPCR?
The receptor changes shape, causing the G-protein’s alpha subunit to exchange GDP for GTP and dissociate from the beta-gamma complex.
What happens after the alpha subunit is activated?
It binds to and regulates target proteins such as ion channels or enzymes like adenylyl cyclase or phospholipase C.
How is the G-protein deactivated?
The alpha subunit hydrolyzes GTP to GDP and reassociates with the beta-gamma complex, returning to the inactive state.
What are enzyme-linked receptors?
Receptors that have an intrinsic enzymatic activity or are directly linked to enzymes inside the cell.
What is the most common type of enzyme-linked receptor?
Receptor tyrosine kinases (RTKs).
How do receptor tyrosine kinases function?
Ligand binding causes two receptor monomers to dimerize and autophosphorylate each other on specific tyrosine residues, activating intracellular signaling pathways.
What are examples of receptor tyrosine kinase ligands?
Insulin, epidermal growth factor, and nerve growth factor.
What are second messengers?
Intracellular molecules that relay and amplify signals from receptors to target molecules within the cell.
List four major second messengers.
Cyclic AMP (cAMP), inositol triphosphate (IP3), diacylglycerol (DAG), and calcium ions (Ca2+).
What enzyme produces cyclic AMP?
Adenylyl cyclase.
What activates adenylyl cyclase?
The Gαs subunit of an activated G-protein.
What does cyclic AMP do inside cells?
It activates protein kinase A (PKA), which phosphorylates target proteins to alter their activity.
How is the cAMP signal terminated?
Phosphodiesterase enzymes break down cAMP into AMP.
What enzyme generates IP3 and DAG?
Phospholipase C (PLC).
What activates phospholipase C?
The Gαq subunit of an activated G-protein.
What happens to IP3 once formed?
It diffuses through the cytosol and binds to IP3 receptors on the endoplasmic reticulum, causing Ca2+ release into the cytoplasm.
What happens to DAG once formed?
It remains in the plasma membrane and activates protein kinase C (PKC).
What does protein kinase C do?
It phosphorylates a wide range of target proteins, altering enzyme activity and gene expression.
How does Ca2+ act as a second messenger?
It binds to calcium-binding proteins such as calmodulin to activate kinases and enzymes that produce cellular responses.
What removes Ca2+ from the cytoplasm to end the signal?
Calcium ATPase pumps and Na+/Ca2+ exchangers that transport calcium back into the endoplasmic reticulum or out of the cell.
How are signals amplified inside cells?
Each step in a signaling cascade activates multiple downstream molecules, producing exponential amplification.
What determines the specificity of a signal?
The type of receptor activated and the intracellular signaling machinery present in the target cell.
What can different cell types do with the same signal molecule?
They can produce different responses depending on which receptors and pathways they express.
Give an example of a molecule that produces different effects in different tissues.
Epinephrine stimulates glycogen breakdown in liver cells but increases heart rate in cardiac cells due to different receptor types.What is synaptic transmission?
What are the two main types of synapses?
Electrical synapses and chemical synapses.
How do electrical synapses transmit signals?
By allowing ions and small molecules to pass directly between cells through gap junctions, resulting in very fast, synchronized transmission.
How do chemical synapses transmit signals?
By releasing neurotransmitters from the presynaptic neuron into the synaptic cleft, which then bind to receptors on the postsynaptic cell.
What is the synaptic cleft?
A narrow extracellular space between the presynaptic terminal and the postsynaptic membrane where neurotransmitters diffuse.
What are the main steps in chemical synaptic transmission?
Neurotransmitter synthesis and storage, release by exocytosis, diffusion across the synaptic cleft, receptor binding, and signal termination.
Where are neurotransmitters stored before release?
In synaptic vesicles within the presynaptic axon terminal.
What triggers neurotransmitter release?
An action potential arriving at the presynaptic terminal causes depolarization and opening of voltage-gated calcium channels.
What happens when calcium enters the presynaptic terminal?
It binds to synaptotagmin proteins on synaptic vesicles, triggering vesicle fusion with the presynaptic membrane through SNARE complexes and exocytosis of neurotransmitters.
What are SNARE proteins?
Vesicle and membrane proteins (such as synaptobrevin, syntaxin, and SNAP-25) that mediate fusion of vesicle membranes with the plasma membrane.
After release, how do neurotransmitters reach receptors?
They diffuse rapidly across the synaptic cleft and bind to specific receptors on the postsynaptic membrane.
What determines whether the postsynaptic response is excitatory or inhibitory?
The type of receptor activated and the ions that flow through the receptor channel.
What happens at an excitatory synapse?
Depolarization occurs due to influx of positive ions such as Na+ or Ca2+, producing an excitatory postsynaptic potential (EPSP).
What happens at an inhibitory synapse?
Hyperpolarization occurs due to efflux of K+ or influx of Cl−, producing an inhibitory postsynaptic potential (IPSP).
How are neurotransmitter effects terminated?
By reuptake into the presynaptic terminal, enzymatic degradation, or diffusion away from the synaptic cleft.
What is reuptake?
The process by which neurotransmitter molecules are actively transported back into the presynaptic neuron for reuse or degradation.
Give an example of a neurotransmitter degraded enzymatically.
Acetylcholine, which is broken down by acetylcholinesterase into acetate and choline.
What happens to choline after acetylcholine is degraded?
It is transported back into the presynaptic neuron to be used for synthesis of new acetylcholine.
What are neurotransmitter receptors?
Proteins located on the postsynaptic membrane that recognize and bind specific neurotransmitters to initiate cellular responses.
What are the two main categories of neurotransmitter receptors?
Ionotropic receptors and metabotropic receptors.
How do ionotropic receptors function?
They contain an ion channel that opens immediately when the neurotransmitter binds, producing a rapid postsynaptic response.
How do metabotropic receptors function?
They are G-protein-coupled receptors that trigger intracellular signaling cascades that open ion channels indirectly or alter cell metabolism.
Which type of receptor produces faster effects?
Ionotropic receptors.
Which type of receptor produces longer-lasting and modulatory effects?
Metabotropic receptors.
What determines the magnitude of the postsynaptic potential?
The amount of neurotransmitter released, the number of receptors activated, and the duration of receptor binding.
What is temporal summation?
When multiple presynaptic action potentials occur in rapid succession, causing EPSPs or IPSPs to add up in time.
What is spatial summation?
When postsynaptic potentials from multiple presynaptic neurons occur simultaneously at different locations on the membrane and combine.
What happens when the sum of EPSPs and IPSPs reaches threshold at the axon hillock?
An action potential is generated in the postsynaptic neuron.
What are the main types of neurotransmitters?
Acetylcholine, biogenic amines, amino acids, neuropeptides, and gases.
What is acetylcholine synthesized from?
Acetyl-CoA and choline, catalyzed by the enzyme choline acetyltransferase.
Where is acetylcholine commonly used?
At neuromuscular junctions, in the autonomic nervous system, and throughout the brain.
What breaks down acetylcholine?
Acetylcholinesterase, an enzyme located in the synaptic cleft.
Name examples of biogenic amine neurotransmitters.
Dopamine, norepinephrine, epinephrine, serotonin, and histamine.
What amino acid are catecholamines derived from?
Tyrosine.
What are the three catecholamines?
Dopamine, norepinephrine, and epinephrine.
What enzyme converts tyrosine to L-DOPA?
Tyrosine hydroxylase.
What enzyme converts L-DOPA to dopamine?
DOPA decarboxylase.
How is norepinephrine synthesized from dopamine?
By dopamine β-hydroxylase.
How is epinephrine synthesized from norepinephrine?
By phenylethanolamine N-methyltransferase (PNMT).