Signal transduction How does one cell send a message to another? How does the cell respond?

1. Signal transduction How does one cell send a message to another? How does the cell respond?

2. A simple signal transduction pathway

3. The cell “signal” is a chemical (can be a gas) It binds to a specific receptor on the target cell Response mechanisms are activated in the target cell Response often involves gene transcription

5. Paracrine signaling cytokines inflammation “Autocrine”- sometimes released chemical acts on the cell itself Endocrine (hormonal) signaling chemical is released into blood or other circulatory fluid often produced by specialized glands

6. Synaptic signaling- in nervous system electrical signal transmitted along specialized nerve cell membrane Conducting cell: neuron Most animals have a nervous system: they vary in complexity but they all a.receive information from the environment b. process the information c. trigger a response (usually from muscles or glands)

7. Types of neurons (in vertebrates): Interneuron- located entirely within CNS, integrates functions in CNS Sensory (from sensory receptor to CNS) Motor (from CNS to effector organ) somatic- stimulates skeletal muscles autonomic- affects smooth and cardiac muscle, also glandular secretion

9. Parts of a neuron Cell body- contains the nucleus and other organelles Dendrites- transmit electrical impulses TO the cell body Axon- transmits impulse AWAY from the cell body axons can be several feet long “Axon hillock” is located near the cell body nerve impulses originate there

10. Structures of neurons sensory retina motor

11. Electrical activity in axons Resting membrane potential in neurons is –70 mV Large negatively charged molecules inside the cell Positively charged ions outside the cell (more Na out than K in) All cells have a membrane potential, but nerve, muscle and a few other types of cells have electrical excitability

12. Permeability to ion changes Occurs in a very small area on the membrane Depolarization- potential difference approaches zero Repolarization- back to the resting potential Hyperpolarization- potential difference increases positive charges leave cell negative charges enter cell

13. Gated ion channels for K and Na (lots of these at axon hillock) Resting cell is more permeable to K than Na Depolarization- membrane becomes permeable to Na, and Na can diffuse into cell After Na gates close, K gates open and K diffuses out of the cell

15. Action potentials When completed, Na/K pumps restore balance of the ions Takes place on a very small part of membrane occurrence is rapid

17. Action potentials are very rapid Inactivation occurs until membranes are repolarized Stronger stimuli stimulate more and more axons (more action potentials are stimulated, but their amplitude does not change)

18. Na channel

19. Conduction of nerve impulses Unmyelinated axon- wave of action potentials spreads along length of axon Amplitude of action potential does not change Myelinated axon- conduction rate is much faster

22. Synapse- connection between a neuron and a second cell From presynaptic to postsynaptic neuron Release of neurotransmitters (chemicals) A few electrical synapses in nervous system, In smooth muscle and heart gap junctions

23. Chemical synapses One-way Presynaptic neuron has synaptic vesicles Fusion of vesicles is mediated by calcium Calmodulin is activated Protein kinase activated Synaptic vesicles fuse with membrane Neurotransmitters diffuse across cleft and bind to receptors

25. Voltage-regulated channels in presynaptic axon Chemically regulated channels in postsynaptic membrane (i.e., binding of neurotransmitter is triggering event) Ion channels are opened, depolarization occurs Can be excitatory or inhibitory Depends on which receptors are engaged Integration of impulses in dendrites and cell body of postsynaptic neuron

26. What are some chemicals that act as neuro- transmitters? Acetylcholine Norepinephrine Dopamine Serotonin They are classified structurally (monoamine, catecholamine, peptide, etc.) and have different functions

27. What do specific neurotransmitters do? Depends on: region of brain affected (where neurotrans- mitters are made) which cells have receptors what kind of receptor: excitatory or inhibitory Example: dopamine (a monoamine, derived from tyrosine)

28. Dopamine is active in different regions of brain Mesolimbic- limbic system; behavior and reward (in midbrain) Many addictive drugs activate these pathways (i.e., enhance dopamine effects; cocaine blocks dopamine reuptake. Addiction occurs because cells become unable to respond to “normal” levels) Nicotine seems to promote dopamine release in this region

29. Schizophrenia: too much dopamine in these pathways Treatments block a particular type of dopamine receptor

30. Dopamine Nigrostriatal- neurons in substantia nigra region of brain involved in initiation of skeletal movement Parkinson’s disease- degeneration of neurons in this region that produce and/or respond to dopamine L-DOPA and MAO inhibitors- increase dopamine transmission

31. Control mechanisms: Neurotransmitter must be cleared quickly or it will overstimulate target cell -Uptake by presynaptic neuron (by transporter proteins) -Degradation by specific enzyme in presynaptic neuron -By post-synaptic neuron (produces an enzyme that degrades the neurotransmitter)

32. Summary • The nervous system is comprised of the • central nervous system (brain, spinal cord) • and the periphery (cranial and spinal nerves) • Periphery is divided into autonomic and motor • neurons. • 2. Cells of the nervous system are glial cells and • neurons. Neurons conduct nervous impulses, • glial cells “support” neurons. • 3. Myelination affects the speed at which impulse • is delivered.

33. 4. Neurons conduct electrical and chemical signaling. Action potential starts at a very small area of the membrane and is conducted along the length of the membrane. Action potential rises with Na influx and falls with K efflux. 5. Speed of transmission is affected by a.) presence of myelin, and b.) the diameter of the neuron. (faster in larger neurons) 6. Neurotransmitters deliver signals across synapses.

34. 7. Sometimes signal is excitatory, sometimes inhibitory. 8. Neurotransmitters are typically small fast- acting molecules. Effect depends on the type of target cell and the type of receptor 9. Regulation is very important. Both presynaptic and postsynaptic cells may produce substances that either promote reuptake of or inactivate the neurotransmitter.