1. BBio 351, January 6, 2016: Homeostasis & cell signaling Outline: 1.Homeostasis and its variations (Sherwood 1.5-1.7) Homeostasis via negative feedback Variations: feedforward control, positive feedback 2.Cell signaling (Sherwood 3.4) Intercellular signaling Intracellular signaling (signal transduction)

2. Homeostasis via negative feedback “Homeo” + “stasis” = In what sense is negative feedback “negative”? 4 general components of a negative feedback system?

3. Which endocrine/reproductive/nervous system variables are regulated via negative feedback? Thyroid hormone levels in blood? Melatonin levels in blood? Glucose levels in blood? Gonadotropin Releasing Hormone (GnRH) levels in blood? Luteinizing Hormone (LH) levels in blood? Membrane potential? Stimulation of photoreceptors in eye?

4. How robust should negative feedback be? Example: blood glucose levels Time in hours [Glucose] in mg/dL 1 2 3 4 5

5. How robust should negative feedback be? Function of insulin = Function of glucagon = Time in hours [Glucose] in mg/dL 1 2 3 4 5

6. Variations on negative feedback: positive feedback Sherwood Fig. 1-10b

7. Sherwood Figure 4-7: Opening of voltage-gated Na + channels

8. Variations on negative feedback: feedforward control Sherwood Figure 1-9b

9. Control of muscle glycolysis? Glycolysis = Feedback hypothesis ATP levels are regulated ATP breakdown products (ADP, P i ) stimulate ATP production by glycolysis Feedforward hypothesis Muscle contraction uses ATP Muscle contraction signal stimulates glycolytic ATP production in anticipation of need for more ATP Test of hypotheses Ischemia: cut off O 2 flow to exercising muscles Ischemia raises ADP and P i … and glycolysis? K.E. Conley et al., Journal of Physiology 1998

10. Control of muscle glycolysis? K.E. Conley et al., Journal of Physiology 1998

11. Cell signaling Signaling  CHANGE What causes a protein to change shape? Intercellular signaling Intracellular signaling (signal transduction)

12. Intercellular signaling F. Martini et al., Fundamentals of Anatomy & Physiology (simpler version of Sherwood Fig. 3-16)

13. Signal transduction across cell membrane Ligand Receptor G protein 2 nd messenger Intracellular proteins

14. Structural classes of signal molecules 3 main groups ShutterStock.com; Wikimedia; Wikipedia

15. Relative size Hydrophobic? Hydrophilic? Location of receptors (Cell surface? Interior?)

16. G proteins: key players in signal transduction Sherwood Figure 3-17c

17. 2 nd messengers: cAMP, cGMP, Ca 2+, etc.

18. Example of signal transduction: insulin receptors Sherwood Figure 3-18

19. Example of signal transduction: glycogen breakdown

20. Example of signal transduction: phototransduction in photoreceptors of retina upload.wikimedia.org/wikipedia/commons/d/de/Phototransduction.png

21. Signal transduction: transcription factors

22. Amplification of signals Sherwood Figure 3-21