Cell Communication- CH 6Cellular Communication- Slide 1Chemicals can be used as signals1. Endocrine signalingGoes through the bloodHormones2. ParacrineSame as endocrine but affects cells in the area3. AutocrineThe cell that sent the signal is the one that receives it4. PheromoneAffects cell in another individual5. Contact dependent6. Synaptic transmission7. Gap junctional couplingMechanisms of hormone action- Slide 21. Hydrophilic hormones-water soluble (cannot cross membrane)need plasma membrane receptor to carry across the plasma membrane1. Peptides2. Proteins3. Amines2. Lipophillic hormones-not water soluble (can cross the membrane) carrier proteins in the plasma to transport aroundThe most abundant protein in the plasma is albumin1. Steroids2. ThyroidPlasma membrane receptorsLipophillic hormoneUse intracellular messengers to alter enzymes, channels, or gene expressionRecently discovered- previously unknown pathwaySignal Transduction- Slide 3Where it says proteins kinases that also includes phosphatasesShows the general mechanism of signal transduction- summaryHow does this amplify the signal?A single molecule binding to a receptor can cause a response because of amplificationTypes of Membrane receptors (4)- Slide 41. Ligand-gated ion channels2. Receptor enzymes3. G-protein coupledprogesterone membrane receptor is this type4. Integrin receptorsIonic Basis of Resting Membrane potential- Slide 51. Na/K ATPase creates ionic concentration gradients2. Membrane selectively permeable to K+ due to open K+ channels3. K+ diffuses outward down the concentration gradient4. Since Na+ and Cl- cannot move to compensate, inside becomes negative5. K+ diffuses inward, down its electrical gradient6. System comes to equilibrium when flux of K+ out = Flux of K+ in7. Na+ and Cl- are not in equilibrium8. Electrochemical gradients (especially for Na+) represent stored potential energy9. Under condition 6, The resting voltage potential (Vm) = RT/zF(ln([K+]out/[K+]in))Three things to remember1. Na+/K+ important low concentration of Na+ inside the cell and high concentration of K+ inside the cell (Pump)2. Resulting distribution of ions3. Almost all cells have open K+ selective ion channels in their membranesAlmost all animal cells have the inside negative compared to the outside1. Ligand-Gated Ion Channels- Slide 6K+ selective channel (Leaky)Open all the timeNot gated- generating resting membrane potentialCalled a leakage ion channelAlmost all animal cells have thisThey actually do have gates but ALWAYS OPENLigand gated Na+ channelThe gate can either plug up the channel or notCan be ligand gated, voltage gated, and mechanically gatedLigand bindingNa+ influxchange in membrane potentialthe resulting change in voltage sensitive protein or Ca2+ sensitive protein causes cellular responseNeurotransmitters, hormones are some examples of ligandsNormally closed until ligand binds2. Receptor Enzymes- Slide 7the receptor is an enzymemost important is the RECEPTOR TYROSINE KINASE (Trk)bind a pair of ligand moleculesexist as monomers but when they attach to two ligands this dimerizes them making them activeauto phosphorylationbinding of accessory proteinsactivation of multiple signal transduction pathways3. G-Protein coupled receptors- Slide 8Neurotransmitter binds receptormakes it possible for the G protein to bind to the intracellular side of the e receptor and this turns the GDP protein to GTP and this activates Adenylyl cyclasesynthesis of cAMP from ATPCalled a stimulatory G proteinInactivation happens when GTP is hydrolyzed to GDPG protein coupled receptors part 2- Slide 9Inhibitory g proteins also can inhibit cAMP productionG proteins can activate and inhibitinhibited by phosphodiesterase which will continue the production of cAMPmultiple controlDAG/IP3 System- Slide 10 (G-protein continued)Example of G protein systemThe enzyme that gets activated is Phospholipase C and the substrate for this is membrane lipidsMetabolizes phosphatidyl inositol which is made into DiacylgycererolCan be metabolized to form a soluble Arachidonic acidOr can activate protein kinase C (calcium dependent) which in the presence of sufficient amount of Ca2+ creates a cellular responseIP3 acts in two different ways1. IP3 binds to IP3 gated Ca2+ channelsIP3 is the ligand for the Ca2+ channels in endoplasmic reticulum so when it binds it lets the Ca2+ out which can bind to CaM kinase which causes cellular response2. Can be converted to IP4enhances Ca2+ channels in plasma membraneincreases Ca2+ influxcan act as a second messengerthis Ca2+ that enters from the outside of the cell is new Ca2+ to cell so it replenishes Ca2+ stores inside the cellsmooth muscle and cardiac muscle this is importantArachidonic Acid System- Slide 11Can come from1. the metabolism of diacylglycerol2. a ligand deactivating a G protein coupled receptorImportanceHas second messenger activity itselfServes as a substrate for the synthesis of a wide variety of 20 carbon eicosanoidsThese are lipid soluble and there are a lot of themThree major categories of lipid soluble paracrines1. Prostaglandinsfrom COX 12. Thromboxanesfrom COX 2mediating vasodilation in the lings and cardiac muscleregulation of blood pressurereleased in injurysignal painProstaglandins have the same functionCOX 1 inhibitorsDrugs that inhibit these molecules are called non steroidal anti inflammatory drugs NSAIDS (ibuprofen, Aleve, aspirin)Can lead to stomach bleeding due to COX 1COX 2 inhibitorsVioxxCelebrexDon’t cause bleeding3. Leukotrienesfrom lipoxygenaseimportant signaling moleculesimportant role in asthmaused by white blood cells4. Integrin Receptors-Slide 12Don’t need to know about theseMembrane bound receptorsNon soluble lipids are the ligands on the outsideOn the inside they bind to the cytoskeletonLink insoluble ECM ligands to insoluble ICM proteinsMany of the effects of integrin receptors is due to their binding to actin on the inside of the cellIntegrin exists as a heterodimer (2 subunits that aren’t identical)In absense of the ligand these dimers are separate in the membrane and are mobile but when ligand is present these diners become clusteredWhat do they do?Blood clottingWound healingRecognition by immune system of specific moleculesCell adhesionCell movementImportant for immune systemGaseous Signal Molecules: NO, CO, and H2S- Slide 13All inhibit inflammation, stimulate vasodilation, promote microvascularizationCant be stored- cant be