Sensory systems: Transduction

1. Sensory systems: Transduction Sensory cells are either • 1. epithelial cells that are induced to specialize in performing some type of sensory transduction or • 2. neurons that grow into the area where the stimuli can be detected.

2. There are a variety of ways to categorize senses: the visceral afferents typically do not provide a conscious sensation and yet provide information for reflex responses.

3. Visual system – Phototransduction Vertebrate photoreceptors: rods and cones

4. Cell types in the primate retina: R, rods C, conesH, horizontalA, AmacrineFMB, IMB, IDB, RB: all are kinds of bipolar cellsMG, midget ganglion cellP, parasol cell

5. Review of anatomy: you may ignore the names of the layers

6. Why upside down? During development, the eye forms as an outgrowth of the brain. The retina (located at the back of the eyeball) is designed so that light must pass through all the layers of neurons before reaching photoreceptors and finally being absorbed by the pigment epithelium.

7. Anatomy of rods and cones

8. Cones have folds and rods have free-floating disks that hold the photoreceptor pigment. The receptor cell membranes have the highest proportion of protein to lipid of any membranes analyzed…

9. Membrane responses to light: Cation channels (permeable to Na+, K+andCa++) areclosed in response to light, which causes membrane hyperpolarization

10. An individual cell’s responses to light are graded: the more light, the greater the response of the cell, up to a limit, at which the response capability of the cell is saturated.

11. What is the link between the presence of light and the cell’s response? The signal must travel • 1. from the altered receptor molecule (rhodopsin-retinal, etc.) which captures energy from the photon, • 2. through second messengers in the cytoplasm • 3. to the outer membrane, to alter the open/closed state of the channels.

12. The chromophore retinal (retinene) is a derivative of Vitamin A. It is bound to the visual system’s 7 transmembrane helix receptors, rhodopsin and the cone pigments

13. The mysterious enzymes will be described later…

14. The cone pigments have different peak absorbancies, with Rhodopsin in the middle, at 496nm

15. Genes for the cone pigments are called S, M and L

16. Molecular basis of trichromatic vision: The G Protein-coupled 7 transmembrane helix receptor proteins have distinct sequences Three cone pigments must all be present to give normal color discrimination. If one pigment is defective or absent (in dichromats) it is most commonly a problem red- green discrimination. Both of these genes are on the X chromosome, and the genes are very similar (L vs M). This explains why distinctions between red and green are easily lost, especially in males, whereas the pigment for blue is different. All three cone pigments are equally different from rhodopsin, the rod pigment.

17. Hyperpolarization of rod by light: the cation channel is gated internally by cyclic GMP, which must bind to open the channel.

18. Ankyrins organize the rod membranes • Ankyrins are intrinsic membrane proteins involved in organizing a variety of specialized membrane domains. • Ankyrin G localizes exclusively to rod outer segments, where it is necessary for targeting of the cGMP-gated channel to the outer segment. • In contrast, ankyrin B is confined to the membrane of the inner segment, where it serves to target Na+/K+ ATPase and the Na+/Ca++ exchanger. • Kizhatil et al., (2009) Science 323: 1614.

19. Response to light: rhodopsin to transducin: • Cation channels are open as long as cyclic GMP is bound to them. • “Dark current” (Na+ through cation channels) is turned off when cyclic GMP is converted to 5’GMP by phosphodiesterase, which is activated by the G protein Transducin.

20. Another view of the messages that regulate membrane channels in the light transduction process

21. Events from previous slide… 1. In the dark, guanyl cyclase is active, generating cyclic GMP. In the presence of bound cyclic GMP, the cation channels are open, admitting both Na+ and, to a lesser extent, Ca++. 2. Photon changes the conformation of the receptor. 3. G protein (transducin) subunit Gα, activates phosphodiesterase, which catalyzes the degradation of cyclic GMP to 5’GMP. As the level of cyclic GMP falls, channels close. 4. Recovery in the dark involves the βγ subunit and a neat molecule called arrestin, which binds to phosphorylated rhodopsin and allows the receptor to recover by competing with the site required for activation of more G proteins (transducin). The details of adjustment of the sensitivity of the system (adaptation) that include arrestin are more than you need to focus on….

22. What is the effect on synaptic communication if the photoreceptor cells hyperpolarize in light? • Hyperpolarization alters the “constitutive” release of neurotransmitter, which leaks, more or less, from the receptor, depending on whether the cell is receiving a lot or a little light. • Turning off a signal is as good as turning it on, to indicate a change to the nervous system, as indicated below. • The transmitter released by the photoreceptors in the dark is referred to as an inhibitory transmitter – it is glutamate.

23. Glutamate is the receptor that the photoreceptors release in the dark

24. When light turns off the release of glutamate, the next cells in the circuit, the bipolar cells, are less hyperpolarized, i.e., relatively depolarized, and they release transmitter that excites the ganglion cells

25. The ganglion cells are constitutively active, firing action potentials in the dark – the level of action potential generation increases in the light. The ganglion cell axons form the optic nerve and their action potentials relay visual information to higher levels of the brain. Note that each cell type has a graded potential – the receptor potential, the synaptic potential of bipolar cells, and the synaptic potential on which action potentials are superimposed (a recording like this would be made in the soma).

26. Conclusions: Visual transduction • Receptor cells, rods and cones, possess visual pigments that are 7 transmembrane receptors that are distorted by reception of light energy (specifically when 11-cis retinal is converted to the all trans form). The activation of the associated G protein leads to changes in the concentration of cyclic GMP, the ligand for the cation channels that are open in the dark. The phosphodiesterase that is activated by the subunit Gα breaks down the cyclic GMP and so channels that lose their ligand will close. The βγ subunit is involved in the recovery process. The (inhibitory) signal relayed to the postsynaptic cell by the receptor is “off” in the light and “on” in the dark. Rebound from inhibition allows the bipolar cells to release transmitter, which excites the ganglion cells, the first cells in the pathway to generate action potentials.