1. 13.4 G Protein-Coupled Receptors That Regulate Ion Channels By: Meredith Clement

2. G Protein Receptors Many Neurotransmitters receptors are ligand gate ion channels ( Ch. 7) but some are G- protein-coupled receptors. The effector protein for some of these types of reactions are Na + or K + ion channels. The binding of the neurotransmitter to one of these receptors causes the channel to open or close.

3. G Protein Receptors Other Neurotransmitters and Odorant and photoreceptors, are G protein receptors that indirectly modulate the activity of ion channels by the actions of second messengers.

4. Cardiac Muscarinic Acetylcholine Receptors Activate a G Protein that Opens K + Channels The Muscarinic Acetylcholine Receptors in cardiac muscle are inhibitory. The activation of this receptor is coupled to a G i protein that leads to the opening of the associated K + channels. The influx of the ions causes hyperpolarization of the plasma membrane. The signal from the receptor is transduced to the effector protein by the released G βγ subunit rather than the G α ·GTP. The G βγ directly activates the ion channel.

5. Figure 13-21

6. G t -Coupled Receptors are Activated by Light Rods and Cones are the primary recipients for visual stimulation. –Rods are Stimulated by weak light like moonlight. –Cones are involved in color vision. –All of these signals are interpreted by the visual cortex in the brain.

7. G t -Coupled Receptors are Activated by Light Rhodopsin is a G protein that is stimulated by light. It is coupled to a trimeric G protein called Transducin (Gt). Rhodopsin consists of the seven spanning protein opsin to which 11-cis-retinal( light absorbing protein) is bonded. Upon absorption of light, Rhodopsin is rapidly converted to all trans isomers which causes a conformational change in the opsin protein that activates it. This is equivalent the conformation change that occurs upon ligand binding by other G protein –coupled receptors. The resulting form of opsin bound to all trans-retinal is called Meta-rhodopsin II or Activated opsin.

8. Activated Opsin is unstable and disassociates back into component parts, releasing opsin and all trans- retinal. In the dark this is converted back to 11-cis –retinal which can rebind with opsin in order to reform rhodopsin. Rod cells in the dark are constantly secreting neurotransmitters. The depolarized state of the membrane cells is due the presence of open non-selective ion channels G t -Coupled Receptors are Activated by Light

9. Adsorption of light by rhodopsin causes these channels to close. The more light absorbed, the more channels that close. This results in a more negative environment and fewer neurotransmitters being released. The human eye is able to see as few as five photons.

10. Figure 13-23

11. Rod Cells Adapt to Varying Levels of Ambient Light Visual Adaptation –Allows contrasting light to be measure instead of absolute amounts of light when going from daylight to a dimly lighted room. –This involves the phosphorylation of activated opsin by rhodopsin kinase. The more sites that are phosphorylated, the less able opsin is to activate G t and thus induce the closing of the cGMP-gated cation channels. –When the level of ambient light is reduced, the opsins become dephosphorylated and the ability to activate G t increases. Resulting in fewer additional photons being necessary to generate a visual signal.

12. Rod Cells Adapt to Varying Levels of Ambient Light At high levels of ambient light the level of opsin phosphorylation is such that the protein β-arrestin binds to the C-terminal segment of opsin. This prevents the interaction of G t with activated opsin which totally blocks the formation of the active G tα ·GTP complex. This results in the in the shutdown of all rod cell activity.

13. Figure 13-26

14. Rod Cells Adapt to Varying Levels of Ambient Light In dark adapted cells the G tα and G βγ subunits are in the outer segments but exposure for 10 minutes to daytime light causes 80% of the subunits to migrate into other cellular compartments. – this results in transducin protein not being able to bind to activated opsin.

15. Figure 13-27