General Introduction to the Course Course outline and schedule Textbook Rules and procedures

1. General Introduction to the Course Course outline and schedule Textbook Rules and procedures Exams and grades What is a discipline? What is physiology? Study of systems while they are alive (Harvey, 1622) Experimental, rather than observational Subdisciplines, especially cell (= general) physiology Cell physiology: basis, advantages, hazards

2. Basic elements of human physiology How does an organ perform its function? How are organs coordinated in time? What are the routes of communication between them? What are the control centers? What are the responses? Homeostasis and homeostatic mechanisms: feedback loops Negative feedback - nearly universal in physiology Positive feedback – usually pathological (“vicious cycles”) Intracellular and extracellular fluids ICF has high K+, low Na+ ECF has low K+, high Na+ So what?

3. Cell membrane (= plasma membrane = plasmalemma) General architecture: Continuous phase = lipid bilayer Discontinuous phase = proteins embedded or floating in it Some proteins extend to both faces (intrinsic proteins) Some proteins only exposed on one side (extrinsic proteins)

4. Movement of molecules and ions in solutions and membranes Fat soluble (“lipophobic”) things cross membranes because they can dissolve into and out of it from either side Water soluble (“lipophobic”) things can cross membranes through aqueous pores if they’re smaller than those pores Special mechanisms for some water soluble things that are too big for the pores

5. Diffusion Random movement of molecules or ions in fluids, caused by thermal agitation: non-directional When two fluids are separated by a membrane, the constituents of that fluid that can cross that membrane by diffusion (fat soluble things and small water soluble things) will do so, in both directions The diffusion rate across the membrane for any substance is defined as the difference between the rates at which the substance crosses the membrane in each direction

6. Factors determining diffusion rates Difference in concentration of the diffusing substance Size of diffusing substance Area across which diffusion can occur Viscosity of the membrane Thickness of the membrane (= length of the diffusion path) Temperature (in Kelvin degrees, not Fahrenheit)

7. Oxygen as an example Cells use oxygen to make energy (ATP), converting it to CO2 Oxygen is carried into the capillaries reversibly bound to hemoglobin, the red protein in red blood cells The oxygen content of cells is reduced because they use it Therefore, if oxygen can get off hemoglobin, diffusion will bring it into the cells Since oxygen binding by hemoglobin is reversible, some is always off hemoglobin and in the plasma Oxygen diffuses into cells because the concentration in cells is lower than it is in plasma

8. Factors influencing rate of oxygen diffusion into cells Oxygen is lipophilic, so it can diffuse through the lipid phase. The cross-sectional area through which it can diffuse is huge Oxygen is a small molecule, so it can diffuse rapidly The diffusion path (across the thickness of cell membranes) is small Temperature is essentially constant (body temperature is about 310 degrees Kelvin) Viscosity of cell membrane lipid is modest, like a fairly thick liquid If cellular rate of oxygen usage goes up (in an exercising muscle, for example), intracellular oxygen level goes down. This increases rate of oxygen diffusion into the cell, so supply nearly keeps up with modest increases in demand

9. Facilitated diffusion Membrane proteins include some that reversibly bind specific lipophobic that are too big to diffuse through pores. These proteins constantly flip back and forth across the membrane, exposing their binding sites (or bound substances) to each side Releasing a bound molecule occurs more readily when it’s exposed to the “downhill” side of the concentration gradient. Binding an unbound molecules occurs more readily on the “uphill” side Hence, the proteins provide a path through which the substance diffuses This is called facilitated diffusion. The role of the carrier protein is to facilitate diffusion of a substance down its concentration gradient

10. Active transport Some substance can cross cell membranes “uphill” in concentration – going from the side where the concentration is low to the side where its concentration is higher This requires energy. It’s called active transport, for that reason. The energy comes from converting ATP to ADP, a reaction that releases small amounts of energy that can be trapped and used to do work in cells Many substances cross cell membranes by active transport. Two that are especially relevant are K+ and Na+. Remember that each has a steep concentration gradient across cell membranes, in opposite directions

11. Na+, K+ and membrane ATPase Na+ and K+ can both diffuse across membranes. How come they don’t diffuse to equilibrium, with equal concentrations in the ICF and ECF? A pump in cell membranes pumps Na+ out and K+ in. It’s got several names – Na+ pump, Na+/K+ ATPase, membrane ATPase, a few others As it creates concentration differences, diffusion in the opposite direction occurs. As concentration differences increase, the diffusion rates increase At some point, the diffusion rate and the pumping rate for each ion are equal. The net movement is equal, the concentrations are stable

15. GLIAL CELLS OLIGODENDROGLIA (in CNS) = SCHWANN CELLS (in PNS) ASTROGLIA MICROGLIA

17. AFFERENT = SENSORY EFFERENT = MOTOR INTERNEURONS

22. 1. Action potentials are “all or none” 2. Absolute and relative refractory periods

23. Conduction Velocity of Action Potentials Non-myelinated Axons = around 1-2 meter/sec; increases with axon diameter Myelinated Axons = around 20 meter/sec

24. Synaptic Transmission “Electrical “ (via gap junctions) Chemical (unique to neurons) Neurotransmitters Presynaptic and Postsynaptic Cells

26. Most common neurotransmitter is acetylcholine (= Ach) Neurons that release it are cholinergic neurons; Ach receptors are cholinergic receptors Next most common neurotransmitters are biogenic amines, the most widespread being epinephrine and norepinephrine. Neurons that release them are aminergic neurons; the receptors are aminergicreceptors. There are many other neurotransmitters; we’ll worry about them later in the course

27. What happens after transmitter binds to receptor? Transmitter is destroyed a. Most common transmitter is acetylcholine ( = Ach), broken into acetate and choline by a plasma enzyme, acetylcholinesterase. b. The choline is then taken up by the axon terminal and used to make more Ach 2. What happens in postsynaptic cell? a. Binding to receptor initiates release of a “second messenger” into the cytoplasm of the postsynaptic cell. This is most often Ca ion, cyclic AMP (= cAMP), or cyclic GMP (= cGMP). b. The second messenger elicits response.

28. Although a neuron releases only one kind of neurotransmitter, a neuron’s soma and dendrites often have many different kinds of receptors. That is, there are usually many neurons that are presynaptic to a single postsynaptic neuron. Some neurotransmitters cause the postsynaptic cell to become more negative (inhibitory; they bring membrane potential further From threshold). Others cause the postsynaptic cell to become less negative (excitatory; they bring the membrane potential closer to threshold). The postsynaptic cell sums all of its inputs. If the result is to make the membrane potential more negative (further from threshold), the change from resting potential is an inhibitory postsynaptic potential (IPSP). If the result is to make the membrane potential less negative, the change is an excitatory postsynaptic potential (EPSP). When the EPSP brings it to threshold, action potentials happen.

29. Summation 1. When an IPSP or EPSP from a particular presynaptic neuron begins before an existing one has decayed, it is called temporal summation 2. When IPSP and/or EPSP are arriving at a postsynaptic cell from more than one presynaptic cell (a very common situation), it is called spatial summation

30. Many neurons being presynaptic to a single postsynaptic neuron is called convergence. Information is converging onto that postsynaptic neuron. There can be as many as 1,000 presynaptic neurons converging onto a single postsynaptic neuron. A single neuron being presynaptic to many postsynaptic neurons (axon terminals branching extensively) is called divergence. Information from the presynaptic neuron is diverging – being spread out. All of neural integration results from combinations of EPSP, IPSP, convergence and divergence in neural networks.