Signaling Molecules (Ligand) Chemicals produced by the body that target cells, causing them to change their behavior. Ex. Parathyroid hormone targeting osteoclasts Include: Hormones and Neurotransmitters

Produced by endocrine glands Amino acid or steroid based Hormones Produced by endocrine glands Amino acid or steroid based Travel long distances Metabotropic

Figure 11.17 Chemical Synapse (1 of 3) Ionotropic or Metabotropic Presynaptic neuron Presynaptic neuron Postsynaptic neuron Action potential arrives at axon terminal. 1 Voltage-gated Ca2+ channels open and Ca2+ enters the axon terminal. 2 Mitochondrion Ca2+ Ca2+ Ca2+ 3 Ca2+ Ca2+ entry causes neurotransmitter- containing synaptic vesicles to release their contents by exocytosis. Synaptic cleft Axon terminal Synaptic vesicles Neurotransmitter diffuses across the synaptic cleft and binds to specific receptors on the postsynaptic membrane. 4 Postsynaptic neuron Pg 409

Figure 11.6a Operation of gated channels. Ionotropic Directly open ion channel Receptor Neurotransmitter chemical attached to receptor Na+ Na+ Chemical binds K+ K+ Metabotropic Indirectly open ion channel Closed Open (a) Chemically (ligand) gated ion channels open when the appropriate neurotransmitter binds to the receptor, allowing (in this case) simultaneous movement of Na+ and K+. Pg 396 a

Receptor Structure -cluster of proteins -ligand and receptor complementary in structure -when ligand binds it triggers a chain reaction in the receptor components -receptors can be found at the surface of a cell or intracellularly Receptor Triggers a change

Ion flow blocked Ions flow Ligand Closed ion channel Open ion channel Figure 11.20 Direct neurotransmitter receptor mechanism: Channel-linked receptors. (Ion) Channel-Linked Receptor Ion flow blocked Ions flow Ligand Closed ion channel Open ion channel Directly opens ion channel. Ligand ionotropic or metabotropic? NT or hormones? © 2013 Pearson Education, Inc. 420

Receptor G protein Enzyme (Adenylate cyclase)

G protein linked (transmembrane) receptor Figure 11.20b Direct and indirect neurotransmitter receptor mechanisms. G protein linked (transmembrane) receptor Neurotransmitter (1st messenger) binds and activates receptor. 1 Closed ion channel Open ion channel Adenylate cyclase Receptor G protein cAMP changes membrane permeability by opening or closing ion channels. 5a Indirectly cAMP activates specific genes. 5c GDP cAMP activates enzymes. 5b Receptor activates G protein. 2 G protein activates adenylate cyclase. 3 Adenylate cyclase converts ATP to cAMP (2nd messenger). 4 Nucleus Active enzyme (b) G-protein linked receptors cause formation of an intracellular second messenger (cyclic AMP in this case) that brings about the cell’s response. Ligand ionotropic or metabotropic? NT or hormone? Pg 420

Intracellular Receptors Figure 16.3 Direct gene activation mechanism of lipid-soluble hormones. Intracellular Receptors Steroid hormone Plasma membrane Extracellular fluid The steroid hormone (estr. Or test.) diffuses through the plasma membrane and binds an intracellular receptor. 1 Cytoplasm Receptor protein Receptor- hormone complex The receptor- hormone complex enters the nucleus. 2 Hormone response elements Nucleus The receptor- hormone complex binds a hormone response element (a specific DNA sequence). 3 DNA Binding initiates transcription of the gene to mRNA. 4 mRNA The mRNA directs protein synthesis. 5 New protein Pg 596

G-protein linked Directly Indirectly

Proteins in cell membrane (leakage) Chloride Potassium Sodium All over neurons Stimulus Axons Dendrites and cell bodies

Figure 11.8 Resting Membrane Potential The concentrations of Na+ and K+ on each side of the membrane are different. Outside cell The Na+ concentration is higher outside the cell. Na+ (140 mM ) K+ (5 mM ) The K+ concentration is higher inside the cell. K+ (140 mM ) Na+ (15 mM ) Na+-K+ ATPases (pumps) maintain the concentration gradients of Na+ and K+ across the membrane. Inside cell The permeabilities of Na+ and K+ across the membrane are different. Suppose a cell has only K+ channels... K+ loss through abundant leakage channels establishes a negative membrane potential. K+ leakage channels K+ K+ Negatively charged anions (nondiffusible proteins) inside cell K+ K+ Cell interior –90 mV Now, let’s add some Na+ channels to our cell... Na+ entry through leakage channels reduces the negative membrane potential slightly. K+ K+ Na+ K K+ Na+ Cell interior –70 mV Finally, let’s add a pump to compensate for leaking ions. Na+-K+ ATPases (pumps) maintain the concentration gradients, resulting in the resting membrane potential. Na+-K+ pump K+ K+ Na+ K+ K+ Na+ Cell interior –70 mV Pg 398

Sequence for stimulating a neuron Resting Membrane Potential  Stimulus  Graded Potential (? mV) (mechanical (causes depolarization or or chemical) hyperpolarization)

Figure 11.9 Depolarization and hyperpolarization of the membrane. Depolarizing stimulus Hyperpolarizing stimulus Inside positive Inside negative Depolarization Resting potential Resting potential Hyper- polarization Time (ms) Time (ms) (a) Depolarization: The membrane potential moves toward 0 mV, the inside becoming less negative (more positive). (b) Hyperpolarization: The membrane potential increases, the inside becoming more negative. Pg 399

Some gated ion channels open Figure 11.10 The spread and decay of a graded (Local) potential. Small change in membrane potential Stimulus Depolarized region NT Na+ -70 -60 Plasma membrane (b) Spread of depolarization: The local currents (black arrows) that are created depolarize adjacent membrane areas and allow the wave of depolarization to spread. (a) Depolarization: A small patch of the membrane (red area) has become depolarized. Some gated ion channels open Distance travels dependant upon strength of stimulus Active area (site of initial depolarization) -True dendrites -Cell bodies -Sensory receptors -Muscle cells –70 Resting potential Distance (a few mm) (c) Decay of membrane potential with distance: Because current is lost through the “leaky” plasma membrane, the voltage declines with distance from the stimulus (the voltage is decremental). Consequently, graded potentials are short-distance signals. Pg 400

Figure 11.4b Structure of a motor neuron. Dendrites (receptive regions) Cell body (biosynthetic center and receptive region) NT Opens chemically gated Na+ channels Nucleolus Na+ -70 Axon (impulse generating and conducting region) -55 Threshold Stimulates the opening of voltage gated ion channels Impulse direction Nucleus Node of Ranvier Nissl bodies Axon terminals (secretory region) Axon hillock Schwann cell (one inter- node) Neurilemma (b) Terminal branches Pg 391

VG Na+ channel VG K+ channel Sodium-Potassium Pumps

Stimulation of a neuron Resting Membrane Potential  Stimulus  Graded Potential  (? mV) (depolarizing) If reaches threshold  Action Potential (?mV) (?mV) Resting Membrane Potential  Stimulus  Graded Potential  (? mV) (hyperpolarizing) Moves away from threshold so No Action Potential!!!

Figure 11.11 Action Potential (1 of 5) The big picture 1 Resting state 2 Depolarization 3 Repolarization VG Na+ channels VG K+ channels 3 4 Hyperpolarization Membrane potential (mV) 2 Action potential Threshold 1 1 4 Stimulus Opens gated Na+ ion channels Time (ms) Pg 402

Figure 11.14 Absolute and relative refractory periods in an AP. Absolute refractory period Relative refractory period Depolarization (Na+ enters) Repolarization (K+ leaves) After-hyperpolarization Toilet bowl Stimulus Time (ms) Pg 405

(b) In an unmyelinated axon, voltage-gated Na+ and K+ Figure 11.15b Action potential propagation in unmyelinated and myelinated axons. Stimulus Voltage-gated ion channel (b) In an unmyelinated axon, voltage-gated Na+ and K+ channels regenerate the action potential at each point along the axon, so voltage does not decay. Conduction is slow because movements of ions and of the gates of channel proteins take time and must occur before voltage regeneration occurs. Pg 406

(c) In a myelinated axon, myelin keeps current in Figure 11.15c Action potential propagation in unmyelinated and myelinated axons. Myelin sheath Stimulus Node of Ranvier 1 mm Myelin sheath (c) In a myelinated axon, myelin keeps current in axons (voltage doesn’t decay much). APs are generated only in the nodes of Ranvier and appear to jump rapidly from node to node. Pg 406

Synapses -Electrical: Use gap junctions. Found in the embryo, cardiac and smooth muscle. -Chemical: Use neurotransmitters at a junction between 2 neurons in a pathway

Figure 3.5c Cell junctions. Plasma membranes of adjacent cells Microvilli Intercellular space Basement membrane Intercellular space Channel between cells (connexon) (c) Gap junctions: Communicating junctions allow ions and small mole- cules to pass from one cell to the next for intercellular communication. Pg 67

Synapses -Electrical: Use gap junctions. Found in the embryo, cardiac and smooth muscle. -Chemical: Use neurotransmitters at a junction between 2 neurons in a pathway.

Figure 11.17 Chemical Synapse (1 of 3) Presynaptic neuron Presynaptic neuron Postsynaptic neuron Action potential arrives at axon terminal. 1 Voltage-gated Ca2+ channels open and Ca2+ enters the axon terminal. 2 Mitochondrion Ca2+ Ca2+ Ca2+ Ca2+ entry causes neurotransmitter- containing synaptic vesicles to release their contents by exocytosis. 3 Ca2+ Synaptic cleft Axon terminal Synaptic vesicles ACH NE Neurotransmitter diffuses across the synaptic cleft and binds to specific receptors on the postsynaptic membrane. 4 Postsynaptic neuron Pg 409

Figure 11.17 Chemical Synapse (2 of 3) Ion movement Graded potential Binding of neurotransmitter opens ion channels, resulting in graded potentials. 5 Ionotropic NT? Metabotropic NT? Pg 409

Figure 11.17 Chemical Synapse (3 of 3) Enzymatic degradation Acetylcholine Degraded by acetylcholinesterase Reuptake Diffusion away from synapse Prozac Neurotransmitter effects are terminated by reuptake through transport proteins, enzymatic degradation, or diffusion away from the synapse. 6 Pg 409

Excitatory Neurotransmitters Generate an EPSP (excitatory post synaptic potential) by causing depolarization of the postsynaptic neuron. Acetylcholine (ionotropic & metabotropic) -most common NT in body Glutamate -Most common excitatory NT in brain

Inhibitory Neurotransmitters Generate an IPSP (inhibitory post synaptic potential) by causing the hyperpolarization of the postsynaptic neuron. Open K+ or Cl- channels* GABA -Most common inhibitory NT in the brain Glycine -Most common inhibitory NT in the spinal cord

Inhibitory Neurotransmitters Can open either Potassium or Chloride ion channels to cause hyperpolarization -70 mV  -80 mV

Clicker Question: Which of the following statements are true. 1 Clicker Question: Which of the following statements are true? 1. The plasma membrane of a neuron is more permeable to potassium ions. 2. An iontropic neurotransmitter would bind to G protein linked receptors to directly open an ion channel. 3. Graded potentials decay as they travel away from the site of stimulus. 4. Opening chloride ion channels should result in an excitatory post synaptic potential (EPSP). A. 1,3,4 B. 2,3,4 C. 1,2,3 D. 1,3

Figure 11.19 Neural integration of EPSPs and IPSPs. Threshold of axon of postsynaptic neuron Resting potential E1 E1 E1 E1 E1 + E2 I1 E1 + I1 Time Time Time Time (a) No summation: 2 stimuli separated in time cause EPSPs that do not add together. (b) Temporal summation: 2 excitatory stimuli close in time cause EPSPs that add together. (c) Spatial summation: 2 simultaneous stimuli at different locations cause EPSPs that add together. (d) Spatial summation of EPSPs and IPSPs: Changes in membane potential can cancel each other out. Excitatory synapse 1 (E1) Excitatory synapse 2 (E2) Summation Inhibitory synapse (I1) Pg 411

Figure 11.22c-d Types of circuits in neuronal pools. Pg 422

Figure 11.22a Types of circuits in neuronal pools. Pg 422

Table 11.2 Comparison of Graded Potentials and Action Potentials (1 of 4) © 2013 Pearson Education, Inc.

Table 11.2 Comparison of Graded Potentials and Action Potentials (2 of 4) © 2013 Pearson Education, Inc.

Table 11.2 Comparison of Graded Potentials and Action Potentials (3 of 4) © 2013 Pearson Education, Inc.

Table 11.2 Comparison of Graded Potentials and Action Potentials (4 of 4) © 2013 Pearson Education, Inc.

Clicker question: Certain psychoactive drugs exert their effects by keeping the concentration of neurotransmitters elevated within the synapse. These drugs could act by _______. A. inhibiting enzymes associated with the synaptic cleft that degrade the neurotransmitter B. inhibiting reuptake of the neurotransmitter by the presynaptic terminal knob C. Doing either a or b D. doing neither a nor b © 2013 Pearson Education, Inc.