Diffusion
The movement of molecules from one location to another across a membrane, will eventually reach equilibrium
moves from high to low
Magnitude of Diffusion
Temp: Higher temp will increase net flux
Mass: the larger the mass the slower the net flux
Surface Area: the larger the surface area the larger the net flux
Medium: denser medium the slower the net flux
Fick's Law
Diffusion rate = Ds ? A ? dC/dX
Size of concentration gradient (dC/dX)
Size of molecule used to calculate the diffusion coefficient (Ds)
Diffusion area (A)
Diffusion through membranes
� Fact: oxygen, carbon dioxide, fatty acids, and steroid hormones are nonpolar molecules that diffuse rapidly through the lipid portions of membranes.
� Fact: polar molecules and hydrophilic do not diffuse readily through the membranes
Diffusion through membranes pt. 2
slower than through water, 10^3 - 10^6 times slower
Diffusion through Ion Channels
Na+, K+, Cl-, and Ca2+ all use specific protein channels to diffuse into and out of cells. Channels are integral membranes
Channel Gating
Process of opening or closing.
Ligand Gating
binding ligans
Voltage gated
changes in membrane potential
mechanically gated
mechanical stress
Transporters
Specific for their ligand.
Transporters do not move as many molecules as channels do because of binding and conformational shifts
� Transporters can be saturated reaches a maximum flux of moleucles
Rate of Transport
Solute concentration
Affinity
Rate of conformational change
Facilitated Diffusion
High to Low, no ATP needed, continues until equilibrium, glucose transporters
Increasing the amount of ATP used in facilitated diffusion would _______ movement of molecules across the cell membrane.
Not Effect
Active Transport
Uses ATP to move against the concentration gradient, transporters called pumps
Primary Active Transport
Na+ major extracellular ion (3 molecules)
K+ major intracellular ion (2 molecules)
Na+/K+ ATPase pump
electronegative potential
requires energy to maintain
Sodium Potassium Pump
1. 3 sodium ions pumped out of the cell
2. 2 potassium ions pumped into the cell
3. creates a deficit of positive ions on the inside of the cell
4. so inside is more negative than the outside
Depolarization
Na+
Repolarization
K+
If Na+/K+ ATPase pumps were increased, which of the following would be most affected?
Resting Membrane Potential
Secondary Active Transport
Uses electrochemical gradient across a plasma membrane as energy source
Transporters have two binding sites:
An ion (e.g., Na+)
Transported molecule (e.g., Glucose)
Contransporters and countertransporters
Osmosis
The net diffusion of water across a membrane
Facilitated by channel proteins called aquaporins
Isotonic
Hypertonic
Hypotonic
Endocytosis
Movement of molecules into the cell via vesicles
There are three general types of endocytosis that may occur in a cell:
1. Fluid endocytosis (pinocytosis)
2. Phagocytosis
3. Receptor-mediated endocytosis
Exocytosis
Movement of molecules out of the cell via vesicles.
Exocytosis performs several functions for cells:
1. Provides a way to replace portions of the plasma membrane that endocytosis has removed
2. Adds new membrane components to the membrane
3. Provides a ro
Epithelial Transport
Molecules entering or leaving the body
Molecules moving between compartments
Molecules must cross a layer(s) of polarized epithelial cells
Movement can occur through cells (transcellular transport) or around cells (paracellular transport)
Paraellular Transport
minimized by tight junctions, Can be regulated by changing "tightness" of junctions by junctional proteins called claudins\
Transcellular Transport
Transcellular transport must cross two membranes so it is a two step process
"Uphill" step that requires energy
"Downhill" step that is passive; no energy required
Can be regulated by adding or removing transporters on cell membrane
Sodium-glucose cotransporter
brings glucose into cell against its gradient using sodium concentration gradient and kinetic energy
GLUT transporter
- transfers glucose to ECF by facilitated diffusion
Sodium-Potassium ATPase pump (Na+-K+ ATPase pump)
- pumps sodium out of the cell to keep intracellular fluid sodium concentrations low
Cell Signaling
1. Production of a signal in one cell (signaling cell)
2. Transport of that signal (chemical messenger) to a target cell
3. The messenger binds to a receptor to transduce signal into the target cell to cause a response
Direct Signaling
-Gap junctions or specialized membrane junctions (tunnels) of adjacent cells.
-Without ever leaving the aqueous envelope of the cell
-Not passive: Opened and closed to regulate communication of substances between cells
Indirect Signaling
Other strategies must be used to send signals to distant cells or to neighboring cells that are not connected by gap junctions.
Steps for Indirect Signaling
1. Release of chemical messenger from signaling cell into environment.
2. Transport of chemical messenger through environment to target cell.
3. Communication of signal to target cell by receptor binding.
Autocrine Signaling
-Messenger moves by diffusion
-When the messenger affects the signaling cell- autocrine
-When the messenger affects nearby cells- paracrine
-Distance limit the rate of diffusion
-Diffusion is insufficient to carry signals to distant target cells.
-Millise
Endocrine Signaling
-Messenger is secreted (hormone)
-Secretory cells of the exocrine and endocrine tissues are often grouped together into structures called glands
-Travel from signaling cell to the target cell carried by circulatory system
-Long distance to target cell
-se
Nervous Signaling
-Reaches terminus trigger release of a chemical messenger called a neurotransmitter
-Bind to receptors on target cell
-Some neurons can secrete neurotransmitters directly into the circulatory system
-Messenger is termed a neurohormone
-Secreted by a neuro
Hydrophobic messengers
can diffuse freely across cell membrane.
Protein carriers to hold them in solution
Hydrophilic messengers
cannot diffuse across the cell membrane
Exocytosis to exit cell
Dissolve to be transport to target cell.
Peptide Messengers
Amino Acid Residue, act as neurotransmitters,
-Peptides: <50 amino acid chains (hydrophobic)
-Proteins: >50 amino acid chains (hydrophilic)
Biogenetic Amine Messengers
-Requires specific receptor because...
-Cannot cross plasma membrane.
-Too large
-Carry a charge at physiological pH
-Released in vascular system when stimulated.
-Carried freely to needed site.
Examples:
Epinephrine (Adrenaline)
Norepinephrine (Noradrena
Hormones
-Not all hormones are perceived by cell surface receptors; most are recognized by intracellular receptors.
-Synthesized from cholesterols.
-Synthesized and secreted from endocrine cells to act on distinct target sites in the human body.
-Commonly referred
Roll of Receptors
FACT: No matter the number of signals outside of cell, if there is no receptor is present for that signal, the cell will not detect it.
FACT: Location of receptors can vary.
FACT: Receptor dysfunction can/will lead to disease.
FACT: Capacity of a cell to
Agonist
Agonist: A ligand that binds to a receptor and it activates the receptor.
-1 millisecond
Antagonist
Antagonist: A ligand that binds to a receptor and it does not activate the receptor
-snake venom
High-affinity ligand binding
results from greater intermolecular force between the ligand and its receptor.
Low-affinity ligand binding
results from lesser intermolecular force between the ligand and its receptor.
G-protein coupled receptors
-G protein-coupled receptors are found only in eukaryotes, yeast and animals.
-Receptors are coupled to trimeric G proteins and function as guanine exchange factors to transduce signal.
-G protein-coupled receptors are involved in many diseases.
-Target o
Ion Linked Channel Receptors
-Membrane bound receptors also called ligand-gated channels.
-Undergo a conformational change when a ligand binds forming a "water tunnel" allowing passage of a specific molecules, such as sodium (Na+) or potassium (K+).
-Transient event: The ion channels
Ion Linked Channel Receptors Clinical Relevance
Diseases include schizophrenia, Parkinson's disease, Alzheimer's disease, epilepsy and autism have been linked to receptor defects.
Nicotinic Acetylcholine Receptor (nAChRs)
-When acetylcholine is bound, alter the receptor's configuration and cause an internal pore to open.
-Pore allows Na+ ions to flow into the cell.
-Inward flow Na+ ions depolarizes the postsynaptic membrane sufficiently to initiate an action potential.
Intracellular Receptors
-Receptors for...
Steroid hormones
Thyroid hormones
-Commonalities: Small and hydrophobic
Allows for free passage into cell
Insoluble in aqueous fluids
-Located in the cytosol and move to the cell nucleus upon activation
-Located in the nucleus waiting fo
Cytosolic
- Hormone binding causes receptor conformational change, freeing the receptor from HSP and the receptor-hormone complex enter the nucleus to act upon transcription factor
Nuclear
- Hormone binding causes receptor conformational change, freeing the receptor from HSP and the receptor-hormone complex can act upon transcription factor
First-Order Feedback
Second-Order Feedback
Third-Order Feedback
Neuron Diagram
Cell Body, Dendrites, Axon
Signal Reception Zones
Signal reception zone (dendrites and the cell body) - receives incoming signals (converts to electrical)
-alter membrane potential, ion channels
Signal Integration Zones
Signal integration zone (axon hillock) - where the cell body meets the axon; if there is a large enough stimulus, the stimuli is converted to an electrical signal (change in membrane potential) that is sent down the axon
Signal Conduction Zones
Signal conduction zone (axon) - neurons wrapped in a myelin sheath transmit the electrical signal
Signal Transmission Zones
Signal transmission zone (collaterals) - swelling at axon terminus where comes in close contact with the target cell; does not touch
-Electrical signal is converted to a chemical signal (neurotransmitter)
Graded Potentials
Graded potentials can either hyperpolarize or depolarize the cell
Depending on the type of ion channel that is opened or closed
Most important ion channels in the dendrites of a neuron are Na+, K+, Cl- and Ca2+ channels
Action Potential Rules
-All-or-none
-Self-propagating
-electric current spreads
-Travel long distances
-Unidirectional Flow
-Absolute Refractory Period: Axon is incapable of generating a new action potential; no matter how strong
-Relative Refractory Period: A new action potent
Supporting Cells In Central Nervous System
Astrocytes - most abundant; controls ionic environment around neurons
Microglia - smallest and least abundant; macrophages of CNS engulfing microbes, injured or dead neurons
Ependymal cells - form epithelium lining central cavity of spinal cord and brain;
Supporting Cells in the Peripheral Nervous System
Satellite cells - surround neuron cell bodies to support and protect
Schwann cells (neurolemmocytes) - surround axons in PNS and form myelin sheaths
Myelin Sheaths
Myelin - lipoprotein that surrounds thicker axons
Structure: Layers consist of concentric layers of plasma membrane of supporting cell
Function: Insulating layer that prevents leakage of electrical current from axon to increase speed of impulse conduction
Synapse
Presynaptic Factors
-Neurotransmitter availability
-Availability of precursor molecules
-Activity of rate-limiting enzyme
-Axon terminal membrane potential (AP firing frequency, duration of AP train)
-Axon terminal calcium concentration
Neurotransmitter Release
-Removal of unbound transmitter
-Diffusion away from cleft (at fast AP firing, won't be enough)
-Enzymatic transformation into inactive substances
-Reuptake pumps
If the reuptake of neurotransmitter at the synaptic cleft was decreased, the signal strength would be __________.
A. Increased
B. Decreased
C. Not Effected
Increased
Postsynaptic Factors
-Electrical potential status
-Excitable (excitatory postsynaptic potential or EPSP) - depolarizing event on postsynaptic cell membrane
-Inhibitory (inhibitory postsynaptic potential or IPSP) - hyperpolarizing event on postsynaptic cell membrane
-Up or dow
Autonomic Nervous System Pathways
1. Preganglionic neuron
Located within the CNS; will synapse with several postganglionic neurons
2. Postganglionic neuron (Autonomic ganglia)
Located in with the PNS and will synapse with the effector organ
At the effector organ, neurotransmitters release
Parasympathetic
Controls routine maintenance or "housekeeping" functions when the body is at rest, "rest and digest
Sympathetic
Controls "fight or flight" response
Increases heart rate, vasoconstriction, respiration, pupil dilation and cell metabolism
Decreases non-essential functions like digestion and waste motility
Differences between Divisions of ANS (1)
-Cell bodies of preganglionic sympathetic and parasympathetic neurons are located in different regions of the CNS.
-Sympathetic: originate in the thoracic and lumbar regions of the spinal cord (thoracolumbar division)
-Parasympathetic: originate either in
Differences Between Division of ANS (2)
-Locations of the ganglia differ
-Sympathetic: found in a chain that runs close to the spinal cord having a short preganglionic neurons and long postganglionic neurons
-Parasympathetic: located close to the effector organ having long preganglionic and sho
Differences Between Division of ANS (3)
-Differing relationship between the preganglionic and postganglionic neurons
-Sympathetic: preganglionic neurons form synapses with 10 or more postganglionic neurons; effects will be widespread
-Parasympathetic: preganglionic neurons form synapses with 3
Dual innervation
- most organs receive input from both sympathetic and parasympathetic nervous systems to regulate effector organs; checks and balances
Antagonistic action
- one is stimulatory and other is inhibitory
Parasympathetic causes bronchioles to constrict by causing smooth muscle to contract
Sympathetic causes dilation through relaxation of smooth muscle
Basal Tone
Basal tone (basal tonic activity) - under resting conditions autonomic neurons will continually signal
Parasympathetic vs Sympathetic
If you were to administer a muscarinic receptor antagonist, like atropine, to a patient for IBS, which additional effect(s) would you expect ro see?
A. Increased heart rate
B. Increased stomach activity
C. Decreased bronchiole dilation
D. Decreased pupil
A
Reflex Arcs of ANS
Example, blood pressure regulation
Receptors detect when blood pressure falls
Send signals to medulla
Increase sympathetic activity
Decrease parasympathetic activity
Adjust heart rate, stroke volume, and vasoconstriction, returning blood pressure back to
Hormones on target cells
3 Basic ways hormones act on target cells:
1. By controlling rates of enzymatic reactions
2. By controlling transport of ions or molecules across cell membranes
3. By controlling gene expression and synthesis of proteins
What makes a chemical a hormone?
1. Secreted by a discrete and identifiable cell or group of cells derived from epithelial cell lineage
2. Secreted into the blood
3. Transported to a distant target and bind to
target receptor
4. Exert their effect at very low
concentrations
Hormone Release
Which of the following statements is INCORRECT regarding hormones?
A. Hormones will be secreted by a discrete group of cells derived from connective tissues
B. Hormones will be secreted into the blood at high concentrations to be transported to a distant
D
Hormone Release: Neurohormones
3 major groups:
1. Catecholamines - tyrosine derived neurohormones (Dopamine, Epinephrine, Norepinephrine)
2. Hypothalamic neurohormones secreted from the posterior pituitary
3. Hypothalamic neurohormones that control hormone release from the anterior pit
Anterior pituitary:
True endocrine gland
Hormones are adenohypophyseal secretions (adeno-relating to glands)
Second order feedback loop system
Posterior pituitary:
False endocrine gland, extension of neural tissue in brain
Hormones made in hypothalamus and neurohypophyseal secretions
Third order feedback loop system
Vasopressin (ADH)
-Released in response to low blood volume (retain water)
-Acts on the collecting ducts in the kidney nephrons to retain water in the body
-Acts to constrict blood vessels
-Decreased release or decreased sensitivity leads to diabetes insipidus (intense thi
Oxytocin
-Plays an important role in the neuroanatomy of social trust, intimacy/sexual reproduction
-During childbirth, it is released in large amounts causing distension of the cervix and uterus
-After childbirth, it facilitates maternal bonding, and lactation an
Anterior Pituitary Neurohormones
-Secretes 6 neurohormones (trophic hormone- controls secretion of other hormones FLAT):
1. Prolactin (PRL)- Milk production
2. Thyrotropin (TSH)- Thyroid stimulating hormone
3. Adrenocorticotropin (ACTH)- Adrenal cortex hormone synthesis and secretion
4.
Cholesterol Derived Hormones
-Examples: estrogen, progesterone, testosterone, thyroid hormones- thyroxin, retinoids (vitamin A), cortisol and vitamin D.
-Not soluble in plasma
-Must bind to a carrier protein, either a globulin or albumin
-Protects hormone from degradation; extending
Somatic and ANS