Cellular Messengers. Intracellular Communication

Transcription

1 Cellular Messengers Intracellular Communication Most common cellular communication is done through extracellular chemical messengers: Ligands Specific in function 1. Paracrines Local messengers (neighboring cells) Distributed by simple diffusion Histamine (local vasodilator) 2. Neurotransmitters Short-range chemical messengers in response to electrical stimulus Acetylcholine 3. Hormones Long-range chemical messengers secreted by endocrine glands in response to a signal Need target cells 4. Neurohormones Released by neurosecretory neurons Stimulated by electric impulse, but transmits a chemical messenger 1

2 Gap junctions Figure 3.7 (1) Page 65 Transient direct linkup of cells Small molecules and ions Paracrine Neurotransmitter Hormone Neurohormone Paracrine secretion Secreting cell Local target cell Figure 3.7 (2) Page 65 Neurotransmitter secretion Local target cell Electrical signal Secreting cell (neuron) Small molecules and ions Paracrine Neurotransmitter Hormone Neurohormone Figure 3.7 (3) Page 65 Hormonal secretion Blood Distant target cell Secreting cell (endocrine cell) Nontarget cell (no receptors) Small molecules and ions Paracrine Neurotransmitter Hormone Neurohormone 2

3 Neurohormone secretion Electrical signal Blood Secreting cell (neuron) Distant target cell Nontarget cell (no receptors) Small molecules and ions Paracrine Neurotransmitter Hormone Neurohormone Incoming signals are accepted through process of signal transduction Extracellular chemical messenger binding with a receptor (first messenger) Process occurs to: 1. Open or close specific channels for ion regulation 2. Transfer signal to intracellular messenger (second messenger) Membrane channels receiving chemical messengers: 1. Leak channels Open all the time (ions leaking out or in) 2. Gated channels (chemical & voltage) Must be triggered to open & require at least one of the following: 1. Binding to specific membrane receptor to the channel 2. Change in electrical status of the membrane 3. Stretching or mechanical deformation G proteins Intermediaries that are activated by binding of messengers (cause channels to open) 3

4 Channel regulation (open or closed) regulates ion flow Nerve conduction Muscle contraction (Ca 2+ ) Second messenger pathways: 2 major pathways 1. Cyclic adenosine monophosphate (cyclic AMP or camp) 2. Calcium First messenger, an extracellular chemical messenger G protein intermediary Plasma membrane ECF Receptor (Binding of extracellular messenger to receptor activates a G protein, the α subunit of which shuttles to and activates adenylyl cyclase) (Converts) Adenylyl ICF cyclase Second messenger (Activates) (Phosphorylates) (Phosphorylation induces protein to change shape) = phosphate Figure 3.8 Page 68 First messenger, an extracellular chemical messenger G protein intermediary Plasma membrane ECF Phospholipase C (Binding of extracellular messenger to receptor activates a G protein, the α subunit of which shuttles to and activates phospholipase C) Receptor (PIP 2 converted by phospholipase C to DAG and IP 3 ) ICF (Mobilizes) Second messenger (Activates) (Induces protein to change shape) PIP 2 = Phosphatidylinositol bisphosphate DAG = Diacylglycerol IP 3 = Inositol trisphosphate 4

5 Molecules in second messenger system Extracellular chemical messenger bound to membrane receptor Activated adenylyl cyclase Cyclic AMP Amplification Total number of molecules 1 Amplification (10) 10 (100) 1,000 Activated protein kinase 1,000 Phosphorylated (activated) protein (e.g., an enzyme) Amplification (100) 100,000 Products of activated enzyme Amplification (100) 10,000,000 Figure 3.10 Page 72 Transport Mechanisms Membrane permeability: 1. Solubility of the particle in lipid Uncharged (nonpolar) molecules (O 2, CO 2 ) 2. Size of particle Does not mean large charged particles cannot cross Glucose? Active & passive forces at work! 5

6 Fick s Law of Diffusion 1. Magnitude of concentration gradient 2. Permeability of membrane to substance 3. Surface area for where diffusion takes place 4. Molecular weight of the substance 5. Distance of diffusion If a substance can permeate the membrane: If the membrane is impermeable to a substance: Figure 3.12 Page 73 Passive diffusion: 1. Concentration gradient 2. Electrical gradient 3. Osmosis Water movement through aquaporins Net diffusion of water 6

7 Diffusion along concentration gradient (Passive) = Solute molecule Diffusion from area A to area B Diffusion from area B to area A Net diffusion (diffusion from area A to area B minus diffusion from area B to area A) Figure 3.11 (1) Page 73 = Solute molecule Diffusion from area A to area B Diffusion from area B to area A No net diffusion (diffusion from area A to area B equals diffusion from area B to area A) Movement along an electrical gradient Positively charged area Negatively charged area Cations (positively charged ions) attracted toward negative area Anions (negatively charged ions) attracted toward positive area Figure 3.13 Page 75 7

8 Osmosis 100% water concentration 0% solute concentration 90% water concentration 10% solute concentration = Water molecule = Solute molecule Figure 3.14 Page 75 Membrane H 2 O Higher H 2 O concentration, lower solute concentration Lower H 2 O concentration, higher solute concentration = Water molecule = Solute molecule Membrane (permeable to both water and solute) Side 1 Side 2 H 2 O H 2 O moves from side 1 to side 2 down its concentration gradient Solute Solute moves from side 2 to side 1 down its concentration gradient Higher H 2 O concentration, lower solute concentration Lower H 2 O concentration, higher solute concentration Water concentrations equal Solute concentrations equal No further net diffusion Steady state exists Side 1 Side 2 = Water molecule = Solute molecule 8

9 Membrane (permeable to H 2 O but impermeable to solute) Side 1 Side 2 H 2 O H 2 O moves from side 1 to side 2 down its concentration gradient Solute unable to move from side 2 to side 1 down its concentration gradient Higher H 2 O concentration, lower solute concentration Lower H 2 O concentration, higher solute concentration Side 1 Side 2 Water concentrations equal Solute concentrations equal No further net diffusion Steady state exists Original level of solutions = Water molecule = Solute molecule Side 1 Side 2 Hydrostatic (fluid) pressure difference Osmosis Hydrostatic pressure = Water molecule = Solute molecule Active or assisted diffusion: 1. Specificity 2. Saturation 3. Competition 9

10 1. Facilitated diffusion (no energy requirement) Uses carrier to assist substance High concentration to low concentration Glucose 2. Active transport Uses carrier to travel against concentration gradient ATP Concentration gradient ECF (High) Phosphorylated conformation Y of carrier Na + Dephosphorylated conformation X of carrier ICF Direction of transport (Low) Step 1 Molecule to be transported Step 2 = phosphate Figure 3.21 Page 82 Na + -K + pump Na + -K + ATPase pump Transports Na + out into ECF Picks up K + from ECF and brings it into ICF 3 Na + out, 2 K + in 3 important roles: 1. Establishes concentration gradient (nerve cell function) 2. Regulates cell volume 3. Energy used is a co-transport (secondary active transport) Glucose and AA across intestinal and kidney cells 10

11 ECF ICF = Sodium (Na + ) = Potassium (K + ) = Phosphate Lumen of intestine No energy required Cotransport carrier Luminal border Epithelial cell lining small intestine Energy required Tight junction Na + K + pump No energy required Glucose carrier Blood vessel = Sodium = Potassium = Glucose = Phosphate Figure 3.23 Page 84 Membrane Potential 11

12 Membrane potential (polarized): Separation of charges across the membrane 1. Created by cations and anions in ICF & ECF 2. Millivolt (mv): 1mV = 1/1000volt Energy required to keep charges separated, allowing a potential for doing work Membrane Membrane has no potential Figure 3.25 (1) Page 87 Membrane Membrane has potential Figure 3.25 (2) Page 87 12

13 Membrane Remainder of fluid electrically neutral Separated charges responsible for potential Remainder of fluid electrically neutral Figure 3.25 (3) Page 87 Plasma membrane Figure 3.25 (4) Page 87 Resting membrane potential: Ions responsible (Na +, K + and A - (intracellular proteins)) Ion EC IC Permeability Na K A Maintained by Na+-K+ pump (20%) 13

14 Plasma membrane ECF ICF Electrical gradient for K + Concentration gradient for K + Figure 3.26 Page 89 E K + = 90 mv Plasma membrane ECF ICF Concentration gradient for Na + Electrical gradient for Na + Figure 3.27 Page 90 E Na + = +60 mv Plasma membrane ECF ICF Relatively large net diffusion of K + outward establishes an E K+ of 90 mv No diffusion of A across membrane Relatively small net diffusion of Na + inward neutralizes some of the potential created by K + alone Resting membrane potential = 70 mv Figure 3.28 Page 91 14

15 ECF (Passive) Na + K + pump (Active) Na + channel K + channel (Passive) (Active) 80% ICF 20% Figure 3.29 Page 92 15