Channeling my Inner Ions

Ok, so I'm not sure that I made this hugely clear in my last blog post but the topics I'll be covering for about the next week will be a little on the detailed side.  It's important to delve into how a neuron works individually before plunging into the complicated world of systems and such.  Most of this will be a bit tough for the layperson to understand unless you've had a grounding in biology but I'm going to try to make today's post more about the interesting ways this information can be applied.

In particular, I want to talk about snails.

No, not these garden variety species you can find in your yard on a spring morning.  I mean the kind that can kill you.

http://www.pbs.org/wnet/nature/episodes/the-venom-cure/video-cone-shell-conotoxins/4416/

I bet you didn't know that there's a whole genus of snails called cone shell snails with deadly venoms, huh?  There are actually hundreds of varieties and each species has it's own unique blend of toxins.  It's used both defensively and for hunting prey as shown in the above videos.

So what the heck does this have to do with ion channels?  Well as you read in my last post, channels are what create the voltage along the cell membrane to send messages down the axon in a neuron.  Here's the thing, without the channels properly functioning you can end up dead.

Ion channel diseases, called channelopathies, are quite numerous.  They can cause heart arrhythmias, epilepsy, osteopetrosis (unwanted extra bone growth), and some kidney diseases.  They can also lead to malignant hyperthermia and paramytonia and a host of other medically diagnosable problems.

In all of these channelopathies, they have one thing in common.  They all have lost proper functioning of an ion channel.  Whether this allows too much of an ion to flow (aka- "leaky channels") or blocks them completely- they both change the permeability to cells to a single type of ion and the phenotypic results are staggering.

Now back to our story of the killer snail.  The cone snail's primary toxin affects the calcium channels of its prey.  It paralyzes the fish and then swallows it whole to be digested- yes, while it's still alive.  One might think the story ends there, but enter the pharmaceutical companies and researchers.  It turns out the con snail is a wealth of pharmacological discoveries waiting to found.  One of the most recent drugs developed from the cone snail's deadly toxin is called "ziconotide."  This drugs blocks calcium receptors, just like the original compound, but does so in a way that serves as a highly effective pain killer.  In fact, ziconotide is between 50 and several thousand times stronger than morphine!

General chemical formula for ziconotide.

So why isn't it dosed out to any patient that comes in with a stubbed toe?  Well such a powerful pain killer comes with its own set of problems.  The drug is not specific enough to target only the calcium channels involved with pain perception. (Keep in mind there are many varieties of every kind of ion channel with different levels of permeability.)  It actually can affect the calcium channels of muscles.

Calcium channels here are used to regulate muscle tone.  So if the conotoxin affects the muscles, it makes them relax.  This isn't a huge issue until you apply it to the smooth muscle of your artery walls.  If those muscles relax too much, your blood pressure will drop dangerously low, possibly to the point where you can't get proper circulation and you die.

Hence, the current research being done with conotoxin involves refining the compound to only affect specific calcium channels.

I bet you didn't think such a "small detail" as ion permeability could make such a big splash in the modern world.  But without knowing how ion channels work, many diseases would be untreatable and many medications unavailable.  I personally enjoy the bigger picture when it comes to biology.  I like knowing how systems work.  But if you're interested to learn more about ion channels, check out this website.  http://clm.utexas.edu/aldrichlab/ Professor Aldrich is a leading authority on the subject and a great lecturer/teacher as well.