PS 333 / NE 333 Sept 6 Synaptic Transmission I Chemical Signaling by and

Part 1

• and concentrations • Gated Ion Channels • Figure 2.11 Distribution of inside and outside a at

Electrical Transmission within a Neuron

Resting : 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

Gated channels are normally closed; they open in response to specific stimuli: • -gated channel—opens when a ligand binds to a . • 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 . 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 it is more difficult to generate an action potential. Chemical Signaling by Neurotransmitters and Hormones

Part 2

• Chemical • 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

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 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 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 at a typical synapse using a classical neurotransmitter Neurotransmitter Receptors and Second- 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 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 (- 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 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 of second messengers Neurotransmitter Release and Inactivation

Termination of synaptic signaling Enzymatic breakdown - transmitters are cleaved by proteins in the cleft. - transmitters are taken up by the cell that released them. Uptake by other cells Figure 3.11 Neurotransmitter inactivation The

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 & Estrogen Testosterone Cortisol The Endocrine System

Peptide hormones have surface receptors. hormones have intracellular receptors. Many function as transcription factors. Figure 3.24 Hormonal signaling