Visual phototransduction

The phototransduction ( visual signal transduction ) refers to the conversion of an external light stimulus (electromagnetic radiation ) in a physiological signal in the organism. It takes place in the retina of the eye in the photoreceptor cells. The principle described here refers to vertebrates, but found in similar form in most other animals instead.

Structure of the receptor cells

The incident light impinges on the eye in the rhodopsin contained in the disc membranes in a high concentration (about 30,000 molecules / square microns ). Disks are flat, tightly packed vesicles inside the outer segment of the receptor cell. They arise as folds from the outer segment membrane. With these rods folds are released from the plasma membrane. They are there as a disk stack in the outer segment. For journals they are retained.

The process of phototransduction takes place mainly in the outer segments of the photoreceptor cells (Fig. 1) instead. It brings together a number of membrane-bound and soluble proteins. Embedded in the disc membranes is found rhodopsin, a G protein - coupled receptor, and a guanylate cyclase. The soluble proteins are involved transducin, a heterotrimeric G- protein, and a cGMP phosphodiesterase. In addition, cGMP - gated Na / Ca2 channels and Na / K exchanger located in the plasma membrane of the outer segments. Said inner segment includes the nucleus, the mitochondria, and Na / K - ATPase, a Na / Ca antiporter and potassium channels and is responsible for the metabolism of the cell.

End of the signal transduction

The signal transduction

The exact sequence is shown in Figure 2:

( 1) The incident light is of 11- cis- retinal, which is bound via a Schiff base linkage in the hydrophobic interior of the opsin to this absorbed ( rhodopsin is a combination of opsin and 11 -cis- retinal). Here, the 11-cis -retinal isomerizes to all-trans- retinal. Then, the rhodopsin is activated via several intermediate states. The activated rhodopsin then binds the alpha subunit of transducin.

(2) This binding is induced in the α - subunit of transducin the exchange of GDP for GTP. This results in the addition to the fact that the β / γ - subunits dissociate and the α - subunit is activated.

(3) The α - subunit of transducin splits the two γ subunits of cGMP phosphodiesterase (PDE) from, it binds and thus activates the PDE. The elimination of a γ subunit would lead to a partial activation of PDE.

( 4) The active PDE now cleaves cGMP to GMP. The declining levels of cGMP inhibits cation influx into the cell. The decreasing Ca2 concentration activates the guanylyl cyclase -activating now enzyme, which in turn activates guanylyl cyclase. This also cGMP is now rebuilt, so it is an equilibrium between assembly and disassembly.

(5) After a time, the intrinsic GTPase cleaves the α - subunit of the GTP to GDP and phosphate. Thus, the γ - subunits of the PDE are released.

(6 ) The thus regenerated α - subunit accumulates again with the β / γ subunit together and forms the original transducin complex.

(7) The γ subunits bind again to the phosphodiesterase and inactivates it. Therefore, no more cGMP is broken down, open the ion channels for Ca2 and Na ions remain and cause a re-polarization of the membrane ( see below).

Regeneration of the system

Activated rhodopsin ( metarhodopsin II also ) indeed decays after some time in its protein moiety opsin and all -trans- retinal. The latter is converted with an isomerase back into 11-cis- retinal, which can then bind to opsin again. However, this process takes too long. Therefore, rhodopsin is inactivated and regenerated via the following reaction sequence: rhodopsin is phosphorylated by rhodopsin kinase a. At the phosphorylated rhodopsin now binds arrestin. Dephosphorylation of opsin through a Ca2 - sensitive phosphatase to dissociation of arrestin, whereupon the rhodopsin can be regenerated with 11-cis -retinal now. The arrestin mediated inactivation prevents activated rhodopsin maintains the signal cascade for too long.

Arrestin also plays a role in light-dark adaptation of the eye by the phosphorylation and thus the arrestin mediated inactivation of rhodopsin increases with the strength and duration of a light stimulus.

There is, as already mentioned above, and a feedback control circuit via the Ca2 - levels in the cell instead of (Fig.2, Fig.3 ), that is involved in the regeneration and adaptation of these processes. If the ion channels closed, does not flow more Ca2 into the cell and the always- Ca2 exchanger transports Ca 2 out of the cell, so that the Ca2 concentration decreases. This causes an increase in the activity of guanylyl cyclase -activating enzyme ( GCAP ) (also: guanylate cyclase -activating enzyme), which is inhibited by Ca2 ions. GCAP activates a cGMP -synthesizing guanylyl cyclase and the low level of cGMP is restored to former level. Na - Ca2 channels open again by the cGMP and Ca2 levels rise again, so that the activity of GCAP and also the guanylyl cyclase decreases again, etc. The result is thus a cGMP balance from degradation by cGMP -PDE and the synthesis of cGMP by guanylyl cyclase that.

The resulting pulse can thus be regulated via Ca2 levels and thus contributes to adaptation to lighting conditions in (eg by pH-dependent Ca2 channels ). However, if the light stimulus over, the activity of PDE stops relatively quickly through the regeneration of transducin (from section to section d a in Figure 2). The guanylyl cyclase now synthesized cGMP, so that its concentration rises back to normal levels. This also re-activated the cGMP-dependent cation transporter and the dark current is flowing again. Also, the Ca2 levels rise again and stops so indirectly the guanylyl cyclase. The system is ready for the next light pulse.

Signal transduction

In the dark, there is a continuous release of the neurotransmitter glutamate in the photoreceptors. This has a stimulating effect on the post- synapses of horizontal and bipolar cells. Due to the closure of cation channels in the cell membrane of the photoreceptor and the subsequent hyperpolarization of the neurotransmitter glutamate is not further distributed. Consequently, the inhibiting ion channels of the horizontal and bipolar cells will be closed. As a result, in the ganglion cell action potentials arise again. This is the actual electrical signal is modulated in the retina, and finally forwarded to the visual center of the brain.

References and sources

Gabriele Tellgmann: Measurement of the enthalpy of reaction of partial reactions of the visual cascade Inaugural 1998.