1 Ch. 6: Communication, Integration & Homeostasis GoalsDescribe cell to cell communicationExplain signal transduction and signal pathwaysReview homeostasis and its control pathways
2 Cell to Cell Communication 75 trillion cells / 2 types of signals4 basic methods of cell to cell communication:Direct cytoplasmic transferContact dependent signals (see IS discussion)Short distance (local)Long distance (through combination of signals)Cell receiving signal = ?Cell receiving signal is target cell
3 Gap Junctions for Direct Signal Transfer Connexins form connexons (channels)Gate open cytoplasmic bridges form functional syncytiumTransfer of electrical and chemical signals (ions and small molecules)Ubiquitous, but particularly in heart and GI tract musclesyn·cy·ti·um (sĭn-sĭsh'ē-əm) n., pl. -cy·ti·a (-sĭsh'ē-ə).A multinucleated mass of cytoplasm that is not separated into individual cells.
4 Local Communication via Paracrines and Autocrines (Chemical signals secreted by cells)Mode of transport ?Examples: Histamine, cytokines, eicosanoidsMany act as both
5 Long Distance Communication Body has two control systems:1) Endocrine system communicates via hormonesSecreted where? Transported where and how?Only react with ____________2) Nervous system uses electrical and chemical signals (APs vs. neurotransmitters and neurohormones)Fig 6-2
6 Cytokines for Local and Long Distance Signaling Act as paracrines, autocrines or hormonesDifference to “real” hormones (sometimes blurry → e.g. EPO):Broader target rangeMade upon demand (no storage in specialized glands)Involved in cell development and immune response
7 Signal Pathways Signal molecule (ligand) Receptor Intracellular signal Target proteinResponse
9 Membrane Receptor Classes Chemically (ligand) gated channelse.g.: nicotinic Ach receptorReceptor enzymesG-protein-coupledSignal transductionChemically gated is also referred to as ligand-gated
10 Direct Mechanisms via Chemically Gated Channel: Nicotinic ACh receptor Most Raid signal pathways change ion flow through channelsChange in ion permeability changes membrane potential
11 Activated receptor alters intracellular molecules to create response Signal TransductionActivated receptor alters intracellular molecules to create responseFirst messenger transducer amplifier second messengerTo transduce = to lead accrosFig 6-8
12 Most Signal Transduction uses G-Protein 100s of G protein-coupled receptor types knownG protein is membrane transducer (binds GDP / GTP name!)Activated G proteinsopen ion channels, oralter intracellular enzyme activity, e.g.: via adenyl cyclase (amplifier) cAMP (2nd messenger) protein kinase activation
13 Activated G-protein Opens Ion Channel Muscarinic ACh receptor
14 Activated G-protein Alters IC Enzyme Activity Epinephrine Signal TransductionCompare to Fig 6-11
15 Novel Signal Molecules: Ca2+ Important IC signalCan enter cell via voltage, ligand, and mechanically gated channelsAlso intracellular storageCa2+ signals lead to various types of eventsMovement of contractile proteinsExocytosis
16 Gases and Lipids as Signal Molecules NO is made from arginineshort acting auto- and paracrinein brain and in blood vesselsCO in nervous tissue and smooth muscleEicosanoids are arachidonic acid derivativesLeukotrienes (important in asthma)Prostanoids (ubiquitous) also important in inflammation etc.
17 Modulation of Signal Pathways Receptors exhibitSaturation, yet Receptors can be up- or down-regulated (grow fewer, grow more)Excess stimulation and drug toleranceSpecificity, yet - Multiple ligands for one receptor: Agonists (e.g. nicotine) vs. antagonists (e.g. tamoxifen)- Multiple receptors for one ligand (see Fig 6-18)CompetitionAberrations in signal transduction _____________ (table 6-3)Many drugs target signal transduction (SERMs, -blockers etc.)
18 In Summary: Receptors Explain Why Chemicals traveling in bloodstream act only on specific tissuesOne chemical can have different effects in different tissues
19 Control Pathways: Response and Feedback Loops Cannon's Postulates (concepts) of properties of homeostatic control systemsNervous regulation of internal environmentTonic level of activity → “how much?”, not ON or OFF - regulated by nerve signal frequencyMany systems have antagonistic controls (insulin/glucagon)Chemical signals can have different effects on different tissuesFailure of homeostasis?Fig 6-20Homeo = similarTonic = continuous
20 Maintenance of Homeostasis Via local or long distance pathwaysLocal: autocrines and paracrinesLong-distance: reflex controlNervousEndocrineboth
22 Receptors (or Sensors) Different meanings for “receptor”: sensory vs. membrane receptorsCan be peripheral or centralConstantly monitor environmentHave threshold (= minimum stimulus necessary to initiate signal)Fig 6-24
23 Afferent PathwayFrom receptor to integrating center Afferent pathways of nervous system: ? Endocrine system has no afferent pathway (stimulus comes directly into endocrine cell)
24 Integrating CenterReceives info about change Interprets multiple inputs and compares them with set-point Determines appropriate response (→ alternative name: control center) Location depends on type of reflex
25 Efferent PathwayFrom integrating center to effector NS electrical and chemical signals ES chemical signals (hormones)
26 Effectors Cells or tissues carrying out response Target for NS: _________________________________Target for ES:__________________________________Target for NS:muscles and glands and some adipose tissuesTarget for ES:any cell with proper receptor
27 Response Loops Begin with Stimulus – End with Response Response takes place at 2 levelsCellular response of target cellOpening of a channelModification of an enzyme etc...Systemic response at organismal levelVasodilation, vasoconstrictionLowering of blood pressure etc....
28 Feedback Loops Modulate the Response Loop Response loop is only half of reflex! Response becomes part of stimulus and feeds back into system.Purpose: keep system near a set point2 types of feedback loops:- feedback loops+ feedback loopsFig 6-26Fig 6-27
29 Homeostasis = Dynamic Equilibrium with Oscillation around Set Point Fig 6-26
30 Negative and Positive Feedback Fig 6-27NOT homeostatic !!Homeostaticexamples
32 The Body’s 2 Control Systems Variation in speed, specificity and duration of actionCompare the different types of reflexes (Table 6-5)Simple (pure) nervousSimple (pure) endocrineNeuro-hormoneNeuro-endocrine (different combos)Fig 6-31
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