Lecture 05 – Extracellular Signal Receptors III

BIOL 5190/6190 Cellular & Molecular Singal TransductionPrepared by Bob Locy

Last modified -13F

Extracellular Signal Receptors II

1. Voltage-gated ion channels (VOCs)2. Ligand-gated ion channels

Ion channel receptors

• Voltage gating

Ion channel receptors

Voltage Operated Channel

• Multisubunit – a1, a2, b, d, & g

• Calcium channel – in PM

• 1a – contains voltage sensor

• a1 – also contains drug binding sites

• Large cytosolic loop, links to synaptic vessicle and/or ryanodine receptors

• a2 – extracellular, regulatory, glycosylation

• d – transmembrane region

• b – intracellular and functions to mediate intracellular effects in different cell types

Ion channel receptors

Detailed structure• A1 has 4 repeat domains

(I-IV) each with 6 MSDs• MSD6 of each domain

makes the pore• b has 4 alpha helices, but

no MSDs• a2 and d (single MSD)

associate via disulfide • g has 4 MSDs• Regulation by protein

kinase A (AKAP18) phosphorylation.

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

Ion channel receptors

Ion channel receptors

Ion channel receptors

Ion channel receptors – ionontrophic glutamate receptors

Ion channel receptors

• Cyclic nucleotide- gated channels

Ion channel receptors

• Calcium signaling and intracellular calcium channels• IP3• Ryanodine

Ion channel receptors

• IP3 Receptor animation

Ion channel receptors

• Ryanodine

Ion channel receptors