BISC 307L 2nd Edition Lecture 4Current LectureCellular CommunicationThere are two basic types of physiological signaling: electrical signals (changes in a cell’s membrane potential), and chemical signals (molecules secreted by cells into the extracellular fluid).4 basic methods of cellular communication:1. Gap junctions: direct cytoplasmic passage of metabolites, 2nd messenger molecules, or ions between adjacent cells2. Contact-dependent signaling: surface molecules on one cell membrane bind to surface molecules on another cell’s membrane3. Long distance communication: combination of electrical signals carried by nerve cells and chemical signals transported in the blooda. Endocrine signaling: cell secretes substances, which can travel through blood circulation to a distant location to bind a target cell with a specific receptor. (ex. hormones)b. Pheromone: chemical signal that triggers a natural response in another individualof the same species 4. Local communication: chemicals diffuse through ECF, limited in distancea. Paracrine signaling: cell secretes substances, which diffuse through the ECF and affect nearby cells. (ex. metabolite or neurotransmitters)b. Autocrine signaling: signal acts on the same cell that secreted it in the first placeSynaptic transmission is a special case that is a combination of long distance and local(paracrine in this case) signaling – electrical signals travel along a neuron until it reaches the end where it istranslated into a chemical signal called a neurotransmitter that is secreted and diffuses across a narrow extracellular space to target a cell and incite a rapid cellular response. Mechanisms of Hormone ActionA hormone is a chemical released by a cell or gland in one part of the body that sends out messages that affect cells in other parts of the organism. They are classified as hydrophilic(water soluble) or lipophilic(lipid soluble). 3 pathways:1. Hydrophilic hormone, which can’t cross the membrane, has to bind to plasma membrane receptors, which is activated and in turn activates an intracellular second messenger system which alters enzyme activity, causing a response (directly or via a change in gene expression)2. Lipophilic hormone, which is not freely soluble in the plasma, needs carrier proteins in the plasma and the ECF to transport it around. The unbound portion can diffuse directly through the plasma membrane and bind to a cytoplasmic or nuclear receptor. Thehormone receptor complex then moves into the nucleus and binds directly to DNA, becoming a transcription factor that activates other transcription factors and directly affects gene expression. For most lipophilic hormones.There are specific carrier proteins (usually globular) that bind it with much higher affinitythan any other hormone. There also exist carrier proteins that can bind indiscriminately to many lipid hormones. (ex. the most abundant protein in the plasma, albumin) 3. Lipophilic hormone that binds to plasma membrane receptors and activate 2nd messenger systems. Discovered while studying progesterone, a lipophilic hormone - theyfound plasma membrane receptors for it. There are similar receptors for testosterone and estrogen.Herrera Side note: Brown fat – highly metabolically active, its in babies because they use it to thermoregulate themselves. Hibernating mammals use it too. Brown fat uses up a lot of energy, a lot of ATP. Discovery of this hormone important. Constitutes a previously unknown mechanismfor the benefits ofexercise on reducing allkinds of bad things. Signal TransductionGeneral mechanism ofsignal transduction – Anextracellular signalmolecule binds to andactivates a plasmamembrane receptorthat activates a 2ndarymessenger system tocreate a response. Important:Amplification occurssuch that a singlemolecule binding to areceptor can cause aphysiological response through an amplifier enzyme (enzyme that activates several more molecules) and secondary messengers.Types of Membrane ReceptorsHere are the types of general membrane receptors –four general types1. Ion channel, can be opened and closed, and have gates – which can swing closed or be opened. This is a ball and chain type, which actually exists. Ligand activates or inactivates the gate, so it is called a ligand-activated channel.2. Receptor-enzyme, within the same molecule it has receptor and enzymatic functions. Has two regions: a receptor region on the extracellular side of the cell membrane, and an enzyme region on the cytoplasmic side. The enzymes of receptor-enzymes are either tyrosine kinase or guanylyl cyclase, the amplifier enzyme that converts GTP to cyclic GMP. 3. G-protein coupled receptors – large and complex family of membrane-spanning proteins that cross the phospholipid bilayer seven times. So it is characterized by having 7 transmembrane segments, and the cytoplasmic tail of the receptor protein is linked to a three-part membrane transducer molecule known as a G protein. The asterisk tells us that progesterone receptor is a G-protein coupled receptor.4. Integrin receptors, which are a little different. Mediate blood clotting, wound repair, cell adhesion and recognition in the immune response, and cell movement during development. Will talk about it more later.Ionic Basis of Resting Membrane Potential3 things you need to remember about cells. 1. Na/K pump is vitally important2. Because of the action of this pump, we have low Na inside, and high Na outside, creatingconcentration gradient3. Almost all cells have open potassium selective ion channels in their membranes (that’s the green block). K pump is vital in all cells, there has to be a way for potassium to get out. Take those 3 conditions, and you will see that almost all animal cells have a negative membrane potential. Bottom line is – if there is an unequal distribution of ions across the cell membrane, and the membrane has open ion channels for one or more of these ions, then an electrical potential difference across the membrane will develop.Ligand Gated Ion ChannelsChannel on left = potassium selective, open at all times so it is called a leakage ion channels*. Leakage potassium channels are ubiquitous –all animal cells have it. The open K channel rapidly comes into equilibrium and internal negativity develops across the membrane.Gated channels use the ball and chain mechanism shown on the right. If the binding of a substance (usually to the EC side, but sometimes the IC side) controls whether the gate is