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Physiology Week 5

by: Alesa Taylor

Physiology Week 5 3014

Alesa Taylor
GPA 3.57

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the end of chapter 5 and beginning of chapter 6
Human Physiology
James Stewart
Class Notes
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This 6 page Class Notes was uploaded by Alesa Taylor on Friday February 12, 2016. The Class Notes belongs to 3014 at Mississippi State University taught by James Stewart in Spring 2016. Since its upload, it has received 32 views.


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Date Created: 02/12/16
Week 5 2/9/16  There are two types of cell signaling: autocrine and paracrine  These messengers are sent out in body through diffusion  Autocrine- when the messenger affects the same cell it was sent from (auto means self)  Paracrine- when the messenger affects nearby cells (para means around) o the distance between cells limits the rate of diffusion- the further cells are apart, the longer it takes for the messages to be absorbed o if the distance is too far, diffusion can be unable to carry the signal o distance DOES NOT play a role in autocrine signaling  endocrine signaling- the messenger is secreted into the whole body (hormone) o Secretory cells of the exocrine and endocrine tissues are often grouped together into structures called glands o The messenger travels from the signaling cell to the target cell carried by the circulatory system  There is a long distance between target cells  Nervous (Neural) signaling- electrical signal that travels across a long distance o when it reaches the terminus trigger a chemical messenger called a neurotransmitter is released  Some neurons can secrete neurotransmitters directly into the circulatory system o Messenger is termed a neurohormone because it is secreted by a neuron but acts like a hormone  The most important distinction among the different systems is the distance that a messenger must travel between cells, and the speed of communication between cells  Autocrine and paracrine- millisecond to a second  Nervous signaling- milliseconds  Endocrine signaling- seconds to minutes, longer lived  Exocrine signaling- pheromones  How the signal is transferred: structure of the messenger affects the way signaling is accomplished  Hydrophobic messengers can diffuse freely across cell membrane. o Protein carriers to hold them in solution  Hydrophilic messengers cannot diffuse across the cell membrane  Exocytosis to exit cell has to dissolve to be transported to the target cell.  There are six main classes of chemicals known to participate in cell signaling in animals 1. Peptide messengers 2. Steroid messengers 3. Biogenic amine messengers 4. Lipid messengers 5. Purine messengers 6. Gas messengers  Peptide messenger types: amino acid residues, peptides, proteins o Amino acid residues- hydrophobic or hydrophilic, acts as neurotransmitters o Peptides- made up of less than 50 amino acid chains, hydrophilic o Proteins- made up of more than 50 amino acid chains, hydrophilic  Peptide messengers are synthesized in ribosomes on the rough ER  Synthesized as large inactive polypeptides called preprohormones  Possess a signal sequence that targets the polypeptide for secretion  Prior to being packaged into secretory vesicles, signal sequence is cleaved from the preprohormone, forming the prohormone (inactive)  Biogenic amine messengers: small water soluble hormones require specific receptors because they are too large to cross the plasma membrane, they carry a charge at physiological pH  Released in vascular system when stimulated.  Carried freely to needed site.  Examples: epinephrine (adrenaline), norepinephrine (noradrenaline), serotonin, histamine  Not all hormones are perceived by cell surface receptors; most are recognized by intracellular receptors. o Synthesized from cholesterols. o Synthesized and secreted from endocrine cells to act on distinct target sites in the human body. o Commonly referred to as Steroid Hormones.  Examples: estrogen, progesterone, testosterone, thyroid hormones- thyroxin, retinoids (vitamin A), cortisol and vitamin D.  Process of cell signaling: o Extracellular signaling molecule (1 messenger) recognized by receptor o Leads to production of small transient signaling inside the cell (2 messenger) o Leads to alter activity of the next component of the transduction pathway o Forms chains of molecules (cascades) where each molecule passes the message to the next o Until the cascade reaches the final signal that causes the cell event  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 recognize a signal will not be constant; receptors change over time.  Four criteria of a functioning receptor: 1. Has to be specific 2. The binding affinity must be high enough to detect the ligand in the concentration found around the cell 3. It must be able to transmit its message into the cell 4. It needs to be turned off once the message is received and acted on (have negative feedback)  Agonist- a ligand that binds to a receptor and activates the receptor  Antagonist- a ligand that binds to a receptor and does not activate the receptor  High-affinity ligand binding results from greater intermolecular force between the ligand and its receptor. o It involves a longer residence time for the ligand at its receptor binding site o It is often physiologically important binding energy that can be used to cause a conformational change in the receptor  Low-affinity ligand binding results from lesser intermolecular force between the ligand and its receptor. o It involves a lesser residence time for the ligand at its receptor binding site  Ligand binding will initiate a series of molecular events…(Note: General Sequence): 1. Binding causes a conformational change in the outer domain of receptor 2. Change is transmitted through the membrane to induce conformational change in the intracellular domain of the receptor 3. Change will either activate or inhibit receptors using intrinsic activity to interact with intracellular proteins  5 main classes of receptors 1. G Protein-coupled Receptors (GPCRs) 2. Ion Channel Linked Receptors 3. Intrinsic Enzymatic Receptors 4. Tyrosine Kinase-linked Receptors 5. Intracellular Receptors  G protein-coupled receptors are found only in eukaryotes, yeast and animals. o The receptors are coupled with trimeric G proteins and function as guanine exchange factors to transduce signal o They are involved in many diseases o They are the target of about 40% of modern medicinal drugs  Membrane bound receptors, also called ligand gated channels, are involved in the detection of neurotransmitters and peptide hormones used in synaptic signaling of electrically excitable cells  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+). o Alters the ion permeability and charge across the plasma membrane  Transient event: The ion channels open for a short time, after which the ligand dissociates from the receptor and the receptor is available once again for a new ligand to bind.  Likely to be the major site at which anesthetic agents and ethanol have their effects, GABA.  Drugs such as barbiturates used to treat insomnia, depression and anxiety have been linked to receptors.  Diseases include schizophrenia, Parkinson’s disease, Alzheimer’s disease, epilepsy and autism have been linked to receptor defects.  Nicotinic Acetylcholine Receptor (nAChRs) o Function: when acetylcholine is bound it alters the receptors configuration and causes an internal pore to open  The pore allows Na+ (sodium ion) to flow into the cell o The inward flow of sodium ions depolarizes the postsynaptic membrane sufficiently to initiate an action potential  Ionotropic receptors, nAChRs are directly linked to ion channels and do not use second messengers.  When an agonist binds to the site, all present subunits undergo a conformational change and the channel is openedand a pore with a diameter of about 0.65 nm opens.  Normally: nAChRs may exist in different interconvertible conformational states.  Agonist binding: stabilizes the receptor in the open position allowing positively charged ions to move across it o It will remain open until the agonist diffuses away. o Usually takes about 1 millisecond  Snake venom (α-neurotoxins)- antagonistics o Bind tightly and noncovalently to nAChRs of skeletal muscles o Block the action of ACh at the postsynaptic membrane, inhibiting ion flow o Leading to paralysis and death 2/11/16  Intracellular Receptors- Receptors for steroid hormones, thyroid hormones, retinoids, fatty acids, prostaglandins, leukotrienes o Commonalities: Small and hydrophobic o Allows for free passage into cell o Insoluble in aqueous fluids o Several different types- focus on Nuclear Receptor Family o All are transcription factors o Depending upon the intracellular steroid hormone they bind, they have two modes of action: they are located in the cytosol and move to the cell nucleus upon activation or they are located in the nucleus waiting for the steroid hormone to enter and activate them o Covered up by heat shock proteins (HSP) which binds the receptor until the hormone is present  Cytosolic- hormone binding causes receptor conformational change, freeing the receptor from HSP and the receptor-hormone complex enters the nucleus to act upon the transcription factor  Nuclear- hormone binding causes receptor conformational change, freeing the receptor from HSP and the receptor-hormone complex can act upon the transcription factor  Local level signals are paracrine signals and autocrine signals  Long distance signals use the nervous system and the endocrine system  Direct Feedback Loop- has to do with the endocrine system only, the endocrine cell senses a change in the extracellular environment and releases a chemical messenger that acts on target cells elsewhere in the body; the endocrine cell acts as the integrating center that interprets the change in the stimulus  First order feedback loops- nervous system becomes involved; a sensory organ perceives a stimulus and sends a signal via the nervous system to an integrating center (the brain) that interprets the signal; neurons then transmit the signal through neurotransmitters/ neurohormones to a specific target organ causing a response  Second order feedback loops- there are 2 steps that link integrating center and the response; the organ senses the stimulus and sends a signal to the integrating center; the integrating center will then send a signal by a neuron telling the neuron to secrete either a neurhormone or neurotransmitter; acts on endocrine glands which will secrete a hormone into the blood and then travels to the target cell to cause a response  Third order feedback loops- 3 steps linking the integrating center and cell response; every step in a response loop may act as a control point over the pathway; the provide the most sophisticated and tightly regulated feedback; the sense organ receives a stimulus and sends a signal to the integrating signal; it sends a signal by a neuron telling the neuron to secrete either a neurohormone or a neurotransmitter; acts on an endocrine gland to secrete a hormone into the blood; the hormone travels to the target cell which induces a response Chapter 6  Excitable cells - rapidly change their membrane potential o This change acts as an electrical signal  There are two types of excitable cells- nerve cells (neurons)- Neurogenic and muscle cells- myogenic  3 important factors that establish membrane potential- 1. The distribution of ions across the plasma membrane (at rest) 2. The permeability of the membrane to these ions (highly permeable to certain ions) 3. The charge on ions that are moving  Goldman Equation - describe the effects these factors have on the membrane potential; predicts the equilibrium potential for certain ions o If the membrane is not permeable to an ion it does not contribute to the membrane potential o If the membrane is highly permeable to an ion, that ion makes a large contribution to the membrane potential o Excitable cells selectively alter their permeability to fit the surrounding ions by opening and closing the gated ion channels in the membrane; changing ion permeability alters the membrane potential and generates electrical signals  The Neuron cell has 3 parts: Cell body- enlarged part of cell that contains the nucleus and organelles, Dendrites- cytoplasmic extensions from the cell body; receive incoming signals Axon- long cytoplasmic extension; specialized for signal transduction.  Neural zones: o Signal reception zone (dendrites and the cell body) – receives incoming signals o 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 o Signal conduction zone (axon) – neurons wrapped in a myelin sheath transmit the electrical signal o Signal transmission zone (collaterals) – swelling at axon terminus where comes in close contact with the target cell; does not touch o Electrical signal is converted to a chemical signal (neurotransmitter)  Dendrites receive incoming signals they convert chemical signals to electrical signals o Causing ion channels to open or close, altering their membrane potential  All electrical sent to dendrites are graded potentials o Vary in magnitude or size (based on stimulus) o Vary in amplitude or strength (based on stimulus) o Strong- ion channels will stay open longer o Weak- ion channels will not stay open as long  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  Goldman equation: o Opening sodium ion or calcium ion channels with depolarize a neuron o Opening a potassium ion or chloride ion will hyperpolarize a neuron  Electronic currents spread because: 1. Leakage of charged ions across the membrane 2. Electrical resistance in the cytoplasm 3. Electrical properties of the membrane  The electric current has the ability to spread through a cell  The strength of the stimulus decreases as distance from the stimulus increases  Short distance signals are like ripples in a pond  Neurons will use action potential to cover greater distances, the action potential must reach threshold potential in order to send out signals


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