How often are we aware of what’s going on in  individual cells in our bodies? We are made  

of trillions of cells, yet notice very few. For  example, neutrophils, a type of white blood cell  

circulate throughout our bodies  protecting us from infection.  

Every hour of our life, billions  of these cells are born and die.  

Yet we don’t notice. In contrast, we are exquisitely  

aware of some cells such as nerve cells  in our eyes and other sensory organs.  

At the back of the eye is the retina, containing  light sensing cells called photoreceptors.  

As discussed in a previous video, our dark-adapted  rods can detect individual photons that activate  

a light-sensing molecule within them. This  means that our visual system has astonishing  

sensitivity: we can detect events affecting not  just a single cell, but individual molecules.  

How we go from activating a single molecule, to  affecting the whole rod so that it can inform  

the brain is through a process of immense and  rapid amplification called phototransduction.  

Phototransduction is the process  by which light is converted into  

electrical signals in photoreceptors. There are 2 types of photoreceptors.  

In this video, we’ll be focusing on the  rods. A similar process occurs in cones,  

but they are less sensitive to individual  photons, requiring much brighter light.  

The light-sensitive region of the rod is here,  where inside there are numerous disc-shaped  

structures stacked atop each other. These discs are membranes that contain millions  

of light-sensing molecules called rhodopsin. What happens when light activates rhodopsin?  

Rhodopsin has two parts: a small molecule called  retinal attached to a protein called opsin. When  

light is absorbed, it results in a rearrangement  of a double bond in the middle to change it from  

this to this. This tiny rearrangement of  retinal pushes on parts of the rhodopsin,  

activating it. The challenge is this:  

This activated rhodopsin must produce a signal  large enough to affect the whole cell.  

In addition to rhodopsin, there are 2 other  important proteins in the disc membranes:  

transducin and phosphodiesterase. After a photon activates a rhodopsin,  

the rhodopsin will activate  transducin proteins it encounters.  

The activated transducin in turn will  bind to and activate phosphodiesterase.  

Effectively, transducin is an intermediary  between rhodopsin and phosphodiesterase.  

Having this chain of activation allows  for amplification. Here’s how:  

Recall from chemistry that molecules  in solution are in constant motion.  

Rhodopsin, water molecules, and all  other molecules in the disc membrane  

are constantly colliding with each other. These collisions bring rhodopsin into contact  

with many transducins, activating them. Each  activated transducin, in turn, will bind to  

and activate phosphodiesterase. In these  visualizations, time is slowed down and  

the violent motions of the molecules are reduced  and simplified so we can see what’s happening.  

This is the first step of the amplification:  one activated rhodopsin leads to many activated  

phosphodiesterase proteins in  a few hundred milliseconds.  

In the dark, rods contain many small  molecules called cyclic GMP.  

Cyclic GMP is also in constant random motion, and  when it encounters activated phosphodiesterase,  

it is converted into another  chemical. For visual simplicity,  

I’m showing the cyclic GMP disappearing when  they encounter activated phosphodiesterase,  

as cyclic GMP is the important  molecule for phototransduction.  

This is the second step of amplification: each  phosphodiesterase will destroy several cyclic  

GMP molecules. Thus, a single activated rhodopsin  will result in the loss of thousands of cyclic  

GMP molecules, resulting in a decrease  in the concentration of cyclic GMP.  

Rods have a constant circulating electric  current in the dark. At one end of the cell,  

positive charge, in the form of ions like  sodium are constantly pumped out of the cell.  

By pumping these positive charges out of the  cell, the cell becomes negatively charged,  

which we’ll show in blue like this.  The cell membrane is an electric  

insulator because ions cannot freely cross it to  reenter the cell. But there are proteins called  

ion channels that are like tunnels allowing  charge to enter the cell at the other end.  

When these ion channels are open, sodium ions  can move through these to reenter the cell.  

Why do they enter the cell? Recall that opposite  charges attract: The cell is slightly negatively  

charged, attracting the positive ions. How does this relate to cyclic GMP? Cyclic  

GMP can bind to these channels. The channels  are open when cyclic GMP is bound, and charge  

can enter the cell. The channels are closed when  cyclic GMP is not bound to the channel, blocking  

the entry of positive charge into the cell.  When cyclic GMP is plentiful, it will bind to  

and unbind from the channel many times per second,  because it is only weakly attached to the channel.  

After a photon activates rhodopsin, thousands of  cGMP molecules are destroyed by phosphodiesterase,  

depleting the cyclic GMP in that part of the  cell. This causes the nearby channels to close,  

reducing the amount of positive charge entering.  The pumps at the other end of the rod keep pushing  

positive charge out of the cell. As a result,  the cell becomes more negatively charged.  

This is the last step of phototransduction:  the loss of thousands of cyclic GMP molecules  

leads to closing of a small fraction of the  channels. This makes the electric potential  

across the cell membrane more negative by  about a millivolt. This electric signal,  

though small, is enough to affect the cell  and be passed on to other nerve cells.  

And all of this occurs in less than a second.  Any one of the millions of rhodopsin molecules  

in the rod can activate this cascade.  Brighter lights made of more photons  

can activate multiple rhodopsins at the same  time. More activated rhodopsins will lead to  

more destruction of cyclic GMP and a greater  electric signal from closing more channels.  

After about a second, the rhodopsin  becomes inactivated, along with transducin  

and phosphodiesterase. Other proteins  return cyclic GMP levels to normal,  

and the channels reopen, returning the rod  to a more positive membrane potential.  

The amplification in the phototransduction cascade  is immense. Realize that the whole process begins  

with a tiny change to a single molecule. No  atoms are added or removed and even the number  

of bonds in the molecule remains the same. Phototransduction relies on random molecular  

encounters between molecules. Sometimes the  rhodopsin will activate more transducins and  

sometimes fewer. But because rhodopsin activates  many molecules, one photon can be distinguished  

from two. Phototransduction is one example  of a more general phenomenon: all of life’s  

chemical reactions rely on similar random  collisions to what you see here. Quantitative  

thinking is essential for understanding the  chemical reactions fundamental to biology.  

I made these animations to let  you see that biological processes  

are physical processes to which we can apply  our physical and mathematical intuition. Also,  

I invite you to be curious: Notice that rhodopsin  and phosphodiesterase are confined to a plane,  

diffusing in 2 dimensions instead of 3. How does  this affect the collision rates? Another question.  

Increasing temperature will increase the speed  of molecules. How might phototransduction be  

different in cold blooded animals compared to  us? What other questions do you have? Put your  

thoughts or questions in the comments section. If  there’s interest, I can make a video discussing  

these, as there’s some surprising biophysics  and math there. If you’re interested in more,  

see my previous video exploring whether the signal  to noise in rods lets us see individual photons.