1. Lecture 05 – Extracellular Signal Receptors III Lecture 05 – Extracellular Signal Receptors III BIOL 5190/6190 Cellular & Molecular Singal Transduction Prepared by Bob Locy Last modified -13F

2. Extracellular Signal Receptors II 1.Voltage-gated ion channels (VOCs) 2.Ligand-gated ion channels

3. Ion channel receptors Voltage gating

4. Ion channel receptors Voltage Operated Channel Multisubunit –  1,  2, , , &  Calcium channel – in PM  – contains voltage sensor  1 – also contains drug binding sites Large cytosolic loop, links to synaptic vessicle and/or ryanodine receptors  2 – extracellular, regulatory, glycosylation  – transmembrane region  – intracellular and functions to mediate intracellular effects in different cell types

5. Ion channel receptors Detailed structure  1 has 4 repeat domains (I-IV) each with 6 MSDs MSD6 of each domain makes the pore  has 4 alpha helices, but no MSDs  2 and  (single MSD) associate via disulfide  has 4 MSDs Regulation by protein kinase A (AKAP18) phosphorylation.

6. Ion channel receptors 1.2 L-type channel (shown) differs in regulation from 1.1 L-type channel PKC Calumodulin (CAM) G-protein regulation of PP2A

7. Ion channel receptors

10. Ion channel receptors – ionontrophic glutamate receptors

11. Ion channel receptors Cyclic nucleotide- gated channels

12. Ion channel receptors Calcium signaling and intracellular calcium channels IP3 Ryanodine

13. Ion channel receptors IP3 Receptor animation

14. Ion channel receptors Ryanodine

15. Ion channel receptors