This is a review of the fantastic work that has been done using classical genetics to understand the electrophysiology (and more) of Paramecium. It is based on designing various types of behavioral screens, for example picking up Paramecia from the top of a flask filled with a solution that normally triggers action potentials. By gravitaxis, Paramecia flow towards the top but this is slowed down by action potentials. Paramecia with defective action potentials are then selected. The mutant is called “Pawn” like the chess piece. It has a defective voltage-gated calcium channel, and therefore no calcium current measurable in voltage-clamp. Quite surprisingly, the voltage-gated potassium current is essentially the same as in the wild type. I find it surprising because the dominant theory about tuning of action potential conductances in neuroscience (e.g. by Marder and colleagues) proposes that the depolarizing and hyperpolarizing conductances are co-tuned by a calcium feedback. This would predict that Pawn should have very low Kv conductance, which is not the case.

Even weirder: if you pick cytoplasm from a wild type cell and inject it into a mutant, even one from a different species (from tetraurelia to caudatum), the transfer “cures” it: after a little while, the cell produces normal action potentials. Apparently, the important protein missing in the cytoplasm of mutants is calmodulin.

There are a number of other types of mutants. For example, some have a defective calcium-activated K+ current. In practice, this technique can be used as channel blockers. This is not strictly equivalent to pharmacological blockers since in principle, other currents or properties may adapt to the mutation (although surprisingly little at least in some cases, as discussed above).