Explain direct and indirect intercellular communication.
Direct - when small ions or molecules pass directly from cell to cell via gap junctions
Indirect - ligand secreted from one cell binds to receptor on adjacent cell
What are the 4 functional classifications of chemical messengers? What are their functions?
Paracrines - secreted from cell then diffuse through ECF to another cell
Autocrines - secreted from cell then acts on itself
Neurotransmitters - secreted from neuronal synapses and bind post-synaptic cells
Hormones - secreted from an endocrine gland INTO THE BLOOD and binds to target cell
What are the five structural classifications of chemical messengers?
1. Amino Acids
Name the amino acid chemical messengers and what system they function with.
* All function as neurotransmitters in the CNS
Name the amine messengers and their derivatives.
Catecholamines - derived from the AA Tyrosine
- Epinephrine, Norepinephrine, Dopamine
Thyroid Hormones - derived from AA Tyrosine
- T3 and T4 aka Thyroxine
Serotonin - derived from tryptophan
Histamine - paracrine derived from histidine
What are the 5 families of steroidal chemical messengers and the prominent group in each family?
Glucocorticoids - cortisol
Mineralocorticoids - aldosterone
Androgens - testosterone
Estrogens - estradiol
Progestins - progesterone
What type of structural chemical messenger is most prominent in the body?
What cells produce eicosanoids? What functional classification are eicosanoids? What are they derived from? What are the 4 types?
Almost every cell in the body ; paracrine ; arachidonic acid
The three factors which mitigate the magnitude of the target cells response to a messenger are?
1. Messenger Concentration
2. # Receptors
3. Affinity of Receptors
What would be a receptor agonist? Antagonist?
Agonist - binding these to receptors causes normal functions
Antagonist - binding these to receptors causing no response, or inhibiting response
Which chemical messengers are lipophillic and which are lipophobic?
Lipophillic - Steroid and Thyroid Hormones
Lipophobic - Proteins, Amino Acids, and Amines excluding thyroid hormones
Membrane bound receptors can mediate activation of what 3 things?
G-Protein Linked receptors
Give a quick example of how an intracellular receptor may work.
1. Hormone binds receptor
2. Hormone - Receptor complex binds DNA at a specific gene
3. Gene Expression creates protein
4. Protein regulates cell activity
Which chemical messengers bind to intracellular receptors?
Lipophillic messengers, aka Thyroid and Steroid hormones
How do channel-linked receptors work? What are the two types of channel-linked receptors?
A ligand binds to a receptor and a flux of ions goes through.
Fast Ligand Gated Channels such as nicotinic receptors where the receptor and channel are the same
Slow Ligand Gated Channels such as muscarinic receptors where the receptor and channel are different and coupled by a G-protein
How do G-Protein Linked Receptors work?
G-Protein is linked to a receptor by the cytoplasmic side of the receptor, and work by coupling the G-Protein Receptor with an Effector, which are either ion-channels or enzymes.
What are the subunits of the G-Protein? What do the subunits do?
Alpha, beta, and gamma
Alpha - has a guanosine binding site which binds GTP and also releasees GDP; this moves to the effector to stimulate a response at an ion-channel or enzyme
Others - can also move to activate effectors but much less likely than the alpha subunit
When is a G-protein activated and inactivated?
They are activated when the alpha subunit is bound to GDP, but are activated when they release GDP and bind GTP
Explain how enzyme-linked receptors work.
A receptor binds a messenger. The receptor's conformation changes, activating tyrosine kinase. Then tyrosine kinase phosphorylates an intercellular protein, which allows the protein to mediate the desired response.
What are secondary messengers? give some examples.
The messengers that come in a signal cascade from an original chemical messenger.
cAMP, calcium for cal-modulin, IP3, and DAG
Name the two important types of G-Protein Linked Enzymes of interest. Which secondary messengers does each produce and what do those secondary messengers activate?
Phospholipase C - IP3, Ca-Calmodulin ; DAG, Protein Kinase C
Adenylate Cyclase - cAMP, Protein Kinase A
What is the major producer of a signal amplification in the adenylate cyclase pathway?
Generation of cAMP and also phosphorylation by protein kinase A
What are the primary and secondary endocrine glands?
Hypothalamus, Thymus Heart, Kidney
Pituitary, Adrenal Liver, Skin
Pineal, Gonads Stomach
Thyroid Small Intestine
Which two chemical messengers does the hypothalamus produce to send to the posterior pituitary or neurohypophysis? Where are they made?
ADH or Vasopressin - made in the paraventricular nucleus of hypothalamus
Oxytocin - made in the supraoptic nucleus
How do the neurohypophysis messengers get from the hypothalamus to the neurohypophysis to the site of action?
They first pass from the paraventricular and supraoptic nuclei, through axons passing through the infundibulum, then to the capillary beds via the axon terminal buds, where they ext through the vein
What signals the release of ADH and Oxytocin, and how are they secreted?
Neuronal stimulation; exocytosis
How does the hypothalamus tell the adenohypophysis to secrete messengers?
Through inhibiting and releasing factors they secrete from their neurosecretory cells into the capillaries, which flow through the H-P portal veins telling the adenohypophysis to secrete!
What are the 3 vectors for blood hormone regulation?
- end product inhibition negative feedback, circadian rhythm
Carrier Protein Binding
- hormones degraded by enzymes; fast for lipophobic, slow for lipophillic
Are there more glial cells or neurons in the brain?
90% of the brain is neuroglial cells
Name the different structural and functional classifications of neurons.
Bipolar, Pseudounipolar, multipolar
Afferent, Efferent, and Interneurons
Describe oligodendrocytes, Schwann cells, astrocytes, microglia, and ependyma.
Oligodendrocytes – form myelin sheaths on CNS axons
Schwann Cells - form myelin sheaths on PNS axons
Astrocytes – contain processes covering capillaries in brain contributing to the blood-brain barrier
Microglia – phagocytic amoeboid cells within CNS
Ependyma – form epithelial lining for many CNS structures
Define the following; nerve fiber, nerve, ganglion, nucleus, tract.
Nerve fiber – (axon) a long process that conducts action potentials toward synapse
Nerve – cable-like collection of nerve fibers
Nucleus – collection of cell bodies located in the CNS
Ganglion – collection of cell bodies located outside the CNS
Tract – collection of nerve fibers connecting regions of the CNS
Resting membrane potential is governed by what?
Ion flow from pumps, leak (non-gated) channels, and open gated ion channels
Current flow equals?
Driving Force / Resistance...
or I = V / R
What is the ion current equation?
ix = gx (Vm – Ex)
ix = ion x current
gx = ion x conductance
Vm = membrane potential
Ex = equilibrium potential for ion x
Depolarization of the neuron is caused by...?
Caused by inward Na+ movement through voltage-gated channels
Repolarization is caused by? What is different about these channels than those important in depolarization?
Caused by outward K+ movement through voltage-gated channels
Voltage-gated K+ channels have only a single gate that opens more slowly than Na+ channels during depolarization
Define spatial and temporal summation of graded potentials.
Temporal - a stimulus is applied repeatedly in rapid succession so that graded potential from first occurrence has not enough time to dissipate before next
Spatial - stimuli from different sources or pre-synaptic neurons occurring close together in time sum
Define absolute and relative refractory periods.
Absolute - time after depolarization and depolarization that no action potential can occur
Relative - occurs directly after the absolute refractory period and lasts 5-15msec; requires a graded potential reaching above normal threshold to occur.
Whats the difference between electrical and chemical synapses?
electrical - allow electrical signals to be transmitted from one neuron to another through gap junctions
Chemical - operate through the release of neurotransmitters that activate signal transduction mechanisms
List the neuron-neuron and neuron-effector anatomical synapses.
Neuron-Neuron: axodendritic, axosomatic, and axoaxonic
Neuron-Effector: muscle and gland
What type of responses can occur at chemical synapses?
Fast Response - inotropic receptors or channel linked receptors