PS 333 / NE 333 Sept 6 Synaptic Transmission I Chemical Signaling by Neurotransmitters and Hormones Part 1 • Reversal potential and Ion concentrations • Gated Ion Channels • Action Potential Figure 2.11 Distribution of ions inside and outside a neuron at resting potential Electrical Transmission within a Neuron Resting membrane potential: Difference in electrical charge between inside and outside of cell. At rest, inside of cell is more negative: –70 millivolts (mV); it is polarized. Electrical Transmission within a Neuron Reversal potential: Aka Nernst Potential or Equilibrium potential. Membrane voltage at which the flow of ions reverses. Na : +55 mV K : -90 mV Cl : -65 mV Ca: +130mV Cells of the Nervous System Gated channels are normally closed; they open in response to specific stimuli: • Ligand-gated channel—opens when a ligand binds to a receptor. • Voltage-gated channel—opens when the electrical potential across the membrane is altered. • Channels can also be gated or altered by phosphorylation. Electrical Transmission within a Neuron Neurons can undergo rapid change in membrane potential — called the action potential. Voltage-gated Na+ channels open at –50 mV, generating a rapid change in membrane potential. Figure 2.14 Stages of the action potential Electrical Transmission within a Neuron Then Na+ channels close and cannot be opened for a fixed refractory period. Action potential lasts only 1 millisecond. During rising phase, changing membrane potential opens voltage-gated K+ channels; K+ moves out of the cell and the membrane returns to resting potential. Electrical Transmission within a Neuron The membrane overshoots resting potential and is hyperpolarized until excess K+ diffuses away. During this time it is more difficult to generate an action potential. Chemical Signaling by Neurotransmitters and Hormones Part 2 • Chemical Synapse • Neurotransmitter Release and Inactivation • Receptors and Second-Messengers Chemical Signaling between Nerve Cells Chemical Synapse – a specialized junction between two cells where neurotransmitter is released. Figure 3.1 Structure of synapses Chemical synapse Figure 3.1 Structure of synapses Chemical synapse Figure 3.1 Structure of synapses Chemical synapse Chemical Signaling between Nerve Cells Synaptic cleft, region between cells ~20- 40nm. Presynaptic terminal -> Synaptic vesicles (~20-40nm) filled with several thousand molecules of a neurotransmitter. Postsynaptic terminal -> Postsynaptic density: Area of the dark membrane facing the synaptic cleft. Figure 3.2 The three types of synaptic connections between neurons Figure 3.2 The three types of synaptic connections between neurons Table 3.1 Major Categories of Neurotransmitters Figure 3.7 Molecular model of a glutamate synaptic vesicle Neurotransmitter Release and Inactivation Stages of Synaptic Signaling 1) Neurotransmitter Release 2) Binding to receptors 3) Termination and Inactivation Figure 3.5 Processes involved in neurotransmission at a typical synapse using a classical neurotransmitter Neurotransmitter Receptors and Second-Messenger Systems There are two major categories of transmitter receptors: ionotropic and metabotropic. Neurotransmitter Receptors and Second-Messenger Systems Ionotropic receptors consist of 4 or 5 subunits with an ion channel in the center. When transmitter binds to the receptor, the channel opens and allows ion flow. Neurotransmitter Receptors and Second-Messenger Systems Some ionotropic receptors are Na+ channels Others allow flow of Ca2+ (and Na+) Others allow flow of Cl–, leading to hyperpolarization (inhibitory) Figure 3.12 Structure and function of ionotropic receptors Neurotransmitter Receptors and Second-Messenger Systems Metabotropic receptors: • consist of one subunit, with 7 trans- membrane domains (7-TM receptors). • work by activating G proteins (G protein- coupled receptors). Figure 3.13 Structure of metabotropic receptors Neurotransmitter Receptors and Second-Messenger Systems G proteins act in two ways: • inhibit or activate ion channels • stimulate or inhibit enzymes that synthesize or break down second messengers. Figure 3.14 Functions of metabotropic receptors Neurotransmitter Receptors and Second-Messenger Systems Second messengers activate protein kinases to cause phosphorylation of other proteins. Phosphorylation alters protein function. Figure 3.16 The mechanism of action of second messengers Neurotransmitter Release and Inactivation Termination of synaptic signaling Enzymatic breakdown - transmitters are cleaved by proteins in the cleft. Reuptake - transmitters are taken up by the cell that released them. Uptake by other cells Figure 3.11 Neurotransmitter inactivation The Endocrine System Hormones are another form of cellular communication used for organ to organ communication. Figure 3.20 Comparison of synaptic and endocrine communication The Endocrine System Epinephrine & Norepinephrine Melatonin Oxytocin Estrogen Testosterone Cortisol The Endocrine System Peptide hormones have surface receptors. Steroid hormones have intracellular receptors. Many function as transcription factors. Figure 3.24 Hormonal signaling .